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Find video protocols related to scientific articles indexed in Pubmed.
miR?886?3p upregulation in clear cell renal cell carcinoma regulates cell migration, proliferation and apoptosis by targeting PITX1.
Int. J. Mol. Med.
PUBLISHED: 09-04-2014
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miR?886?3p has been discovered to be involved in the oncogenesis, progression and metastasis of several types of human cancer. The aim of the present study was to identify the biological function of miR?886?3p in clear cell renal cell carcinoma (ccRCC) and to determine its possible molecular mechanisms. miR?886?3p was found to be significantly upregulated in ccRCC tissues (P<0.05), in accordance with a previous sequencing result. Functional experiments revealed that forced downregulation of miR?886?3p significantly inhibited cellular migration, suppressed cell proliferation and induced cell apoptosis of renal cancer cells. Paired?like homeodomain 1 (PITX1), which has been identified as a tumor suppressor, was found to be downregulated in ccRCC tissues and identified as a target gene of miR?886?3p. Further experiments demonstrated that the protein level, and not the mRNA level, of PITX1 was significantly decreased or increased when miR?886?3p was upregulated or downregulated, respectively, indicating that miR?886?3p acted as an oncogene by directly regulating the protein expression of PITX1 at a post?transcriptional level. In conclusion, this study revealed that miR?886?3p was upregulated in ccRCC and was involved in cellular migration, proliferation and apoptosis of renal cancer cells by directly targeting the tumor suppressor gene, PITX1.
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Deficient human ?-defensin 1 underlies male infertility associated with poor sperm motility and genital tract infection.
Sci Transl Med
PUBLISHED: 08-15-2014
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Genital tract infection and reduced sperm motility are considered two pivotal etiological factors for male infertility associated with leukocytospermia and asthenozoospermia, respectively. We demonstrate that the amount of human ?-defensin 1 (DEFB1) in sperm from infertile men exhibiting either leukocytospermia or asthenozoospermia, both of which are associated with reduced motility and reduced bactericidal activity in sperm, is much lower compared to that in normal fertile sperm. Interference with DEFB1 function also decreases both motility and bactericidal activity in normal sperm, whereas treatment with recombinant DEFB1 markedly restores DEFB1 expression, bactericidal activity, sperm quality, and egg-penetrating ability in sperm from both asthenozoospermia and leukocytospermia patients. DEFB1 interacts with chemokine receptor type 6 (CCR6) in sperm and triggers Ca(2+) mobilization, which is important for sperm motility. Interference with CCR6 function also reduces motility and bactericidal activity of normal sperm. The present finding explains a common defect in male infertility associated with both asthenozoospermia and leukocytospermia, indicating a dual role of DEFB1 in defending male fertility. These results also suggest that the expression of DEFB1 and CCR6 may have diagnostic potential and that treatment of defective sperm with recombinant DEFB1 protein may be a feasible therapeutic approach for male infertility associated with poor sperm motility and genital tract infection.
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Expression and clinical significance of RCDG1 in renal cell carcinoma: a novel renal cancer?associated gene.
Mol Med Rep
PUBLISHED: 07-16-2014
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Recently identified molecular tumor markers have numerous potential applications in the diagnosis, therapy and prognostic prediction of renal cell carcinoma (RCC). Through bioinformatics?based screening approaches together with validation of western blot and immunohistochemical data, the present study identified a novel renal cancer?associated gene, preliminarily named Renal Cancer Differentiation Gene 1 (RCDG1), originally known as chromosome 4 open reading frame 46 (C4orf46). RCDG1 expression was evaluated by western blot analysis of RCC and adjacent normal tissues, renal cancer cell lines and normal kidney HEK293T cells. Additionally, RCDG1 expression was assessed in 124 RCC paraffin sections, including 92 paired adjacent normal tissues, by immunohistochemistry. The results showed that RCDG1 was significantly downregulated in RCC tissues as compared with normal adjacent tissues (P<0.001), and the expression of RCDG1 in clear cell (cc) RCC tissues was significantly lower as compared with that of non?ccRCC tissues (P=0.005). Furthermore, statistical analysis revealed RCDG1 expression was negatively correlated with the Fuhrman grade in ccRCC (P=0.008). A reduction in RCDG1 expression may be associated with the oncogenesis of RCC and the differentiation of ccRCC. Further studies may provide more information about the function of RCDG1 gene in RCC.
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Global gene expression profiling identifies ALDH2, CCNE1 and SMAD3 as potential prognostic markers in upper tract urothelial carcinoma.
BMC Cancer
PUBLISHED: 06-16-2014
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Current knowledge about the molecular properties and prognostic markers of upper tract urothelial carcinoma (UTUC) is sparse and often based on bladder urothelial carcinoma (UC), which is thought to share common risk factors with UTUC. However, studies have suggested that differences exist regarding tumor behavior and molecular biology of these cancers, comprehensive investigations are needed to guide the clinical management of UTUC. In recent years, massively parallel sequencing has allowed insights into the biology of many cancers, and molecular prognostic markers based on this approach are rapidly emerging. The goal of this study was to characterize the gene expression patterns of UTUC using massively parallel sequencing, and identify potential molecular markers for prognosis in patients with UTUC.
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Hsa-miR-1 downregulates long non-coding RNA urothelial cancer associated 1 in bladder cancer.
Tumour Biol.
PUBLISHED: 04-25-2014
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MicroRNAs (miRNAs) are known to mainly target protein-coding genes at post-transcriptional level, resulting in mRNA destabilization and/or translational repression. Long non-coding RNAs (lncRNAs) are emerging as a novel set of targets for miRNAs. Here, we report that downregulated hsa-miR-1 and upregulated lncRNA urothelial cancer associated 1 (UCA1) were inversely expressed in bladder cancer. Hsa-miR-1 decreased the expression of UCA1 in bladder cancer cells in an Ago2-slicer-dependent manner. The binding site between UCA1 and hsa-miR-1 was confirmed. Overexpression of hsa-miR-1 inhibited bladder cancer cell growth, induced apoptosis, and decreased cell motility. Knockdown of UCA1 expression phenocopied the effects of upregulation of hsa-miR-1. Transfection of UCA1 expression vector partly reversed the changes caused by transfection of pre-miR-1 plasmids. This study provides evidence for hsa-miR-1 to play tumor suppressive roles via downregulating lncRNA UCA1 in bladder cancer, which may have potential therapeutic significance.
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Association analysis identifies new risk loci for non-obstructive azoospermia in Chinese men.
Nat Commun
PUBLISHED: 04-11-2014
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Male factor infertility affects one-sixth of couples worldwide, and non-obstructive azoospermia (NOA) is one of the most severe forms. Our previous genome-wide association study (GWAS) identified three susceptibility loci for NOA in Han Chinese men. Here we test promising associations in an extended three-stage validation using 3,608 NOA cases and 5,909 controls to identify additional risk loci. We find strong evidence of three NOA susceptibility loci (P<5.0 × 10(-8)) at 6p21.32 (rs7194, P=3.76 × 10(-19)), 10q25.3 (rs7099208, P=6.41 × 10(-14)) and 6p12.2 (rs13206743, P=3.69 × 10(-8)), as well as one locus approaching genome-wide significance at 1q42.13 (rs3000811, P=7.26 × 10(-8)). In addition, we investigate the phenotypic effect of the related gene (gek, orthologous to CDC42BPA) at 1q42.13 on male fertility using a Drosophila model. These results advance our understanding of the genetic susceptibility to NOA and provide insights into its pathogenic mechanism.
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Identification of miR?125a?5p as a tumor suppressor of renal cell carcinoma, regulating cellular proliferation, migration and apoptosis.
Mol Med Rep
PUBLISHED: 04-03-2014
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miR?125a?5p has been previously described as a tumor suppressor in numerous malignancies, however the expression and function of miR?125a?5p in renal cell carcinoma (RCC) remains to be elucidated. In the present study, to explore the potential role of miR?125a?5p in RCC, quantitative polymerase chain reaction was used to determine the expression levels of miR?125a?5p in renal cancer tissues. The influence of miR?125a?5p on cell proliferation, migration and apoptosis was also determined, using an MTT assay, a wound scratch assay and flow cytometry, respectively. The expression of miR?125a?5p was shown to be decreased in RCC and the restoration of miR?125a?5p by synthetic mimics was shown to suppress cell proliferation and migration, and induce apoptosis. The present results indicate that miR?125a?5p may function as a tumor suppressor in RCC. The present study is, to the best of our knowledge, the first to demonstrate the downregulation of miR?125a?5p in RCC, and to show the role it has in affecting cellular proliferation, migration and apoptosis. Further research is needed to define the target genes of miR?125a?5p and explore the potential of miR?125a?5p as a diagnostic or a prognostic biomarker for RCC.
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Investigating urachal carcinoma for more than 15 years.
Oncol Lett
PUBLISHED: 03-09-2014
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Urachal carcinomas are rare bladder malignances, which usually present at an advanced stage with a high risk of distant metastases and a poor prognosis. To improve understanding of this uncommon carcinoma, a retrospective review was conducted for the cases observed at Peking University Shenzhen Hospital and Peking University First Hospital. The clinical outcomes were analyzed for 17 patients with a diagnosis of urachal cancer, who were admitted to Peking University Shenzhen Hospital (Shenzhen, China) and Peking University First Hospital (Beijing, China) between 1998 and 2013. The TNM staging system was used to predict outcomes. Among the 17 study patients, there were 10 males and seven females, with a median age at diagnosis of 50 years. A total of four (23%) patients presented with lymph node or distant metastasis. The median overall survival time for all stages was 57.6 months, with five patients (38.4%) alive for more than five years following treatment. The application of the TNM staging system demonstrated a median survival time of 6.2 years for stage I/II patients, compared with a median survival of 1.8 years (log-rank, P<0.001) for patients with advanced disease (stages III and IV). In addition, no significant correlation was observed between tumor size and age, and survival. In conclusion, urachal carcinomas are usually locally advanced at presentation. Surgical excision remains the predominant choice of treatment and lymph node dissection is not required unless lymph node involvement is confirmed by preoperative examination. The current results indicated that the most significant predictor of prognosis was the tumor grade.
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Expression of methionine adenosyltransferase 2A in renal cell carcinomas and potential mechanism for kidney carcinogenesis.
BMC Cancer
PUBLISHED: 03-06-2014
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Methionine adenosyltransferase 2A (MAT2A) is an enzyme that catalyzes the formation of S-adenosylmethionine (SAMe) by joining methionine and ATP. SAMe is a methyl donor for transmethylation and has an important role for DNA and/or protein methylation. MAT2A is expressed widely in many tissues especially in kidney. Several studies have demonstrated that there are abnormal expressions of MAT2A in several kinds of cancers such as liver and colon cancers. But the relationship of MAT2A between renal cell carcinomas (RCC) is less understood.
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Identification of Hsf1 as a novel androgen receptor-regulated gene in mouse Sertoli cells.
Mol. Reprod. Dev.
PUBLISHED: 03-03-2014
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Androgen signaling plays a crucial role in spermatogenesis, yet few downstream targets for this signaling pathway have been identified. In the current study, we found that the expression of heat-shock transcription factor 1 (Hsf1) was increased in the testes of Sertoli cell-selective androgen receptor knockout (S-AR(-/y) ) mice compared with wild-type mice by quantitative real-time PCR, and the expression of HSF1 in the S-AR(-/y) Sertoli cells was significantly increased, based on immunofluorescence analysis. In vitro cell-culture studies showed that testosterone repressed the expression of Hsf1 in TM4 cells, a mouse Sertoli cell line. Moreover, a luciferase assay, electrophoretic mobility shift assay, and chromatin immunoprecipitation assay showed that testosterone repressed Hsf1 expression by facilitating the binding of androgen receptor to the Hsf1 promoter. Our experiments also demonstrated that testosterone-mediated inhibition of Hsf1 transcription down-regulated the expression of heat-shock proteins HSP105 and HSP60. Taken together, these results reveal that Hsf1 is a novel target of androgen receptor in mouse Sertoli cells, and testosterone and its receptor regulate the process of spermatogenesis partially by inhibiting Hsf1 expression.
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Quantitation of rare circulating tumor cells by folate receptor ? ligand-targeted PCR in bladder transitional cell carcinoma and its potential diagnostic significance.
Tumour Biol.
PUBLISHED: 02-28-2014
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Numerous attempts for detection of circulating tumor cells (CTC) have been made to develop reliable assays for early diagnosis of cancers. In this study, we validated the application of folate receptor ? (FR?) as the tumor marker to detect CTC through tumor-specific ligand PCR (LT-PCR) and assessed its utility for diagnosis of bladder transitional cell carcinoma (TCC). Immunohistochemistry for FR? was performed on ten bladder TCC tissues. Enzyme-linked immunosorbent assay (ELISA) for FR? was performed on both urine and serum specimens from bladder TCC patients (n = 64 and n = 20, respectively) and healthy volunteers (n = 20 and n = 23, respectively). Western blot analysis and qRT-PCR were performed to confirm the expression of FR? in bladder TCC cells. CTC values in 3-mL peripheral blood were measured in 57 bladder TCC patients, 48 healthy volunteers, and 15 subjects with benign urologic pathologies by the folate receptor ? ligand-targeted PCR. We found that FR? protein was overexpressed in both bladder TCC cells and tissues. The levels of FR? mRNA were also much higher in bladder cancer cell lines 5637 and SW780 than those of leukocyte. Values of FR? were higher in both serum and urine specimens of bladder TCC patients than those of control. CTC values were also higher in 3-mL peripheral blood of bladder TCC patients than those of control (median 26.5 Cu/3 mL vs 14.0 Cu/3 mL). Area under the receiver operating characteristic (ROC) curve for bladder TCC detection was 0.819, 95 % CI (0.738-0.883). At the cutoff value of 15.43 Cu/3 mL, the sensitivity and the specificity for detecting bladder cancer are 82.14 and 61.9 %, respectively. We concluded that quantitation of CTCs through FR? ligand-PCR could be a promising method for noninvasive diagnosis of bladder TCC.
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MicroRNA-451a is associated with cell proliferation, migration and apoptosis in renal cell carcinoma.
Mol Med Rep
PUBLISHED: 02-15-2014
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MicroRNAs (miRNAs) are an important class of small, non?coding RNA molecules that regulate gene expression at the transcriptional or post?transcriptional level. They are involved in apoptosis, proliferation and migration and are known to have an important role in many types of cancer. Aberrant expression of miRNA?451a (miR?451a) has previously been reported in tumors, however its role in renal cell carcinoma (RCC) is currently unknown. The aim of the present study was to investigate the role of miR?451a in RCC. The expression of miR?451a was analyzed in 50 paired RCC and normal tissues by quantitative polymerase chain reaction. Furthermore, the effects of miR?451a on cell migration, proliferation and apoptosis were evaluated, using migration scratch, MTT and flow cytometric assays. The present study demonstrated that miR?451a was upregulated in RCC, as compared with paired normal tissues (P<0.05). Downregulation of miR?451a using a synthesized inhibitor, significantly suppressed cell migration and proliferation, and induced apoptosis of renal cancer cells in vitro, as compared with a negative control (P<0.05). In the present study, it was determined that miR?451a may have an important role as a tumor enhancer in RCC. These results imply that miR?451a may be a promising therapeutic target for the treatment of RCC.
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Adenomatoid tumors of the testis: A report of two cases and review of the literature.
Oncol Lett
PUBLISHED: 01-30-2014
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Adenomatoid tumors are rare benign neoplasms that normally occur in the scrotum. The clinical symptoms and routine examinations mean that it is difficult to distinguish adenomatoid tumors from malignant intratesticular solid tumors, which may result in unnecessary orchidectomies. The present report describes two adenomatoid tumor patients treated between 2006 and 2013 at the Peking University Shenzhen Hospital who presented with an asymptomatic mass in the scrotum. Based on thorough analysis of clinical features, blood, radiological images and intra-operative findings, limited local excisions were performed, revealing adenomatoid tumors of the testis on pathological examination. The patients were followed up and exhibit no recurrence at the time of writing. The present report also summarizes the morphological and immunohistochemical features of paratesticular tumors and reviews the literature to improve understanding of these rare lesions and assist in accurate diagnosis.
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CMTM3 inhibits human testicular cancer cell growth through inducing cell-cycle arrest and apoptosis.
PLoS ONE
PUBLISHED: 01-01-2014
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Human CMTM3 has been proposed as a putative tumor suppressor gene. The loss of CMTM3 has been found in several carcinomas. However, the regulation of CMTM3 expression and its function in tumor progression remain largely unknown. Here, we investigated the regulation of CMTM3 expression, function and molecular mechanism in human testicular cancer cells. CMTM3 was frequently downregulated or silenced in testicular cancer cell lines and tumor tissues but highly expressed in normal testis tissues. The re-expression of CMTM3 significantly suppressed the colony formation, proliferation, and migration capacity of testicular cancer cells by inducing a G2 cell cycle arrest and apoptosis. Moreover, the re-expression of CMTM3 activated the transcription of p53, induced p53 accumulation, up-regulated the expression of p21, and increased the cleavage of caspase 9, 8, 3, and PARP. The downregulation of CMTM3 in clinical tumor tissues was associated with the methylation of a single CpG site located within the Sp1/Sp3-responsive region of the core promoter. These results indicate that CMTM3 can function as tumor suppressor through the induction of a G2 cell cycle arrest and apoptosis. CMTM3 is thus involved in testicular cancer pathogenesis, and it is frequently at least partially silenced by the methylation of a single, specific CpG site in tumor tissues.
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Expressions of miR-15a and its target gene HSPA1B in the spermatozoa of patients with varicocele.
Reproduction
PUBLISHED: 01-01-2014
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Hyperthermia and oxidative stresses are the two central elements contributing to varicocele-related sperm damage. Growing evidence indicates that microRNAs (miRNAs) are involved in the regulation of the heat and oxidative stress responses. In this study, we analyzed the expressions of several stress-related miRNAs in the sperm and found that the expression of miR-15a was significantly decreased in patients with varicocele compared with the control. Furthermore, miR-15a repressed the expression of HSPA1B, which is a typical stress-induced chaperone protein, through directly binding its 3'-UTR. The expressions of miR-15a and HSPA1B exhibited an inverse correlation in sperm. Our results provide a valuable insight into the varicocele-related sperm impairment and male infertility, and may help to develop potential therapeutic targets and novel biomarkers for male infertility.
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Telomerase Reverse Transcriptase Gene Promoter Mutations Help Discern the Origin of Urogenital Tumors: A Genomic and Molecular Study.
Eur. Urol.
PUBLISHED: 10-18-2013
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Activation of telomerase can be observed in almost all human tumor histotypes and detection of the urinary telomerase activities is useful for the diagnosis and surveillance of bladder cancer. In this study, we screened, by Sanger sequencing, 302 patients with various urogenital cancers for somatic mutations in the promoter of the telomerase reverse transcriptase (TERT) gene and determined the clinical relevance of TERT promoter mutations in urogenital cancer. In vitro assays were also performed to evaluate the functional influence of the discovered mutations. We found that the frequencies of somatic mutations in the TERT promoter varied substantially between different types of urogenital tumors (range: 0-63.7%), with urothelial carcinomas showing the highest mutation frequency and prostate cancer showing no mutation. The mutations upregulated the expression of TERT and enhanced the invasiveness of the tumor cells. The mutations were more prevalent in older patients with invasive diseases and advanced tumor stages, and were associated with significantly shorter survival time. Moreover, we also observed a significant co-occurrence of mutations between the TERT promoter and the tumor protein 51/retinoblastoma1 (TP53/RB1) signaling pathway. Hence, TERT promoter mutations may serve as important markers for the differential diagnosis and surveillance of urogenital tumors.
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Prostatic Schistosoma japonicum with atypical immunophenotyping of individual glandular tubes: a case report and review of the literature.
Southeast Asian J. Trop. Med. Public Health
PUBLISHED: 09-21-2013
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There are few cases of prostatic schistosomiasis. Here we report a case of Schistosoma japonicum of the prostate, in which the immunophenotyping of individual glandular tubes was atypical. Whether the S. japonicum infection contributed to the lesion or not is unknown. We suspect the lesion was a sign of early precancerous hyperplasia. Follow-up of this patient may give clues about the relationship between schistosomiasis and prostate cancer. This is the first case report of prostatic S. japonicum in the English literatures. A review of the literature is carried out.
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The EDA-containing cellular fibronectin induces epithelial-mesenchymal transition in lung cancer cells through integrin ?9?1-mediated activation of PI3-K/AKT and Erk1/2.
Carcinogenesis
PUBLISHED: 08-08-2013
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Cellular fibronectin (cFN) is one of the main components of tissue extracellular matrices and is involved in multiple physiologic and pathologic processes such as embryogenesis, wound healing, inflammation and tumor progression. The function of fibronectin in regulating normal cell adhesion and migration is well documented, but its function in cancer progression is only partially unraveled. We have reported previously that fibronectin stimulates the proliferation and survival of non-small lung carcinoma cells through upregulation of pro-oncogenic signals related to cyclooxygenase-2/phosphatidylinositol-3-kinase/protein kinase B (COX-2/PI3-K/AKT)/mammalian target of rapamycin triggered by activation of the integrin ?5?1. Here, we extend these studies by showing that fibronectin promotes epithelial-mesenchymal transition (EMT) in lung cancer cells. We found that cFN, but not plasma fibronectin or type 1 collagen, induces lung carcinoma cell scattering in vitro, promotes cell migration and invasion of Matrigel and stimulates the expression of the mesenchymal marker ?-smooth muscle actin while decreasing the expression of the epithelial marker E-cadherin through PI3-K and Erk pathways. Interestingly, the extra domain A (EDA) within cFN was found to be crucial for this process, as confirmed by testing cells overexpressing EDA or cells exposed to EDA-containing matrices. We found that the integrin ?9, but not ?5, mediated cFN-induced EMT as silencing integrin ?9 neutralized cFN-induced EMT. Overall, our findings show that the EDA domain within cFN induces EMT in lung carcinoma cells through integrin ?9-mediated activation of PI3-K and Erk.
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Multilayered molecular profiling supported the monoclonal origin of metastatic renal cell carcinoma.
Int. J. Cancer
PUBLISHED: 07-10-2013
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Primary renal cell carcinomas (pRCCs) have a high degree of intratumoral heterogeneity and are composed of multiple distinct subclones. However, it remains largely unknown that whether metastatic renal cell carcinomas (mRCCs) also have startling intratumoral heterogeneity or whether development of mRCCs is due to early dissemination or late diagnosis. To decipher the evolution of mRCC, we analyzed the multilayered molecular profiles of pRCC, local invasion of the vena cava (IVC), and distant metastasis to the brain (MB) from the same patient using whole-genome sequencing, whole-exome sequencing, DNA methylome profiling, and transcriptome sequencing. We found that mRCC had a lower degree of heterogeneity than pRCC and was likely to result from recent clonal expansion of a rare, advantageous subclone. Consequently, some key pathways that are targeted by clinically available drugs showed distinct expression patterns between pRCC and mRCC. From the genetic distances between different tumor subclones, we estimated that the progeny subclone giving rise to distant metastasis took over half a decade to acquire the full potential of metastasis since the birth of the subclone that evolved into IVC. Our evidence supported that mRCC was monoclonal and distant metastasis occurred late during renal cancer progression. Thus, there was a broad window for early detection of circulating tumor cells and future targeted treatments for patients with mRCCs should rely on the molecular profiles of metastases.
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Dendritic cells in semen of infertile men: association with sperm quality and inflammatory status of the epididymis.
Fertil. Steril.
PUBLISHED: 06-25-2013
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To determine whether dendritic cells (DCs) are present in semen and whether their abundance and activation correlate with sperm quality and inflammatory status of the male genital tract.
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Synthesizing oncogenic signal-processing systems that function as both "signal counters" and "signal blockers" in cancer cells.
Mol Biosyst
PUBLISHED: 04-26-2013
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RNA-protein interaction plays a significant role in regulating eukaryotic translation. This phenomenon raises questions about the ability of artificial biological systems to take the advantage of protein-RNA interaction. Here, we designed an oncogenic signal-processing system expressing both a Renilla luciferase reporter gene controlled by RNA-protein interaction in its 5-untranslated region (5-UTR) and a Firefly luciferase normalization gene. To test the ability of the designed system, we then constructed vectors targeting the nuclear factor-?B (NF-?B) or the ?-catenin signal. We found that the inhibition (%) of luciferase expression was correlated to the targeted protein content, allowing quantitative measurement of oncogenic signal intensity in cancer cells. The systems inhibited the expression of oncogenic signal downstream genes and induced bladder cancer cell proliferation inhibition and apoptosis without affecting normal urothelial cells. Compared to traditional methods (ELISA and quantitative immunoblotting), the bio-systems provided highly accurate, consistent, and reproducible quantification of protein signals and were able to discriminate between cancerous and non-cancerous cells. In conclusion, the synthetic systems function as both "signal counters" and "signal blockers" in cancer cells. This approach provides a synthetic biology platform for oncogenic signal measurement and cancer treatment.
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Whole-genome and whole-exome sequencing of bladder cancer identifies frequent alterations in genes involved in sister chromatid cohesion and segregation.
Nat. Genet.
PUBLISHED: 01-15-2013
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Bladder cancer is one of the most common cancers worldwide, with transitional cell carcinoma (TCC) being the predominant form. Here we report a genomic analysis of TCC by both whole-genome and whole-exome sequencing of 99 individuals with TCC. Beyond confirming recurrent mutations in genes previously identified as being mutated in TCC, we identified additional altered genes and pathways that were implicated in TCC. Notably, we discovered frequent alterations in STAG2 and ESPL1, two genes involved in the sister chromatid cohesion and segregation (SCCS) process. Furthermore, we also detected a recurrent fusion involving FGFR3 and TACC3, another component of SCCS, by transcriptome sequencing of 42 DNA-sequenced tumors. Overall, 32 of the 99 tumors (32%) harbored genetic alterations in the SCCS process. Our analysis provides evidence that genetic alterations affecting the SCCS process may be involved in bladder tumorigenesis and identifies a new therapeutic possibility for bladder cancer.
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Decreased expression of cystic fibrosis transmembrane conductance regulator impairs sperm quality in aged men.
Reproduction
PUBLISHED: 01-01-2013
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Sperm quality declines with aging; however, the underlying molecular mechanism remains elusive. The cystic fibrosis transmembrane conductance regulator (CFTR) has been shown to play an essential role in fertilizing capacity of sperm and male fertility. This study aimed to investigate the involvement of age-dependent CFTR downregulation in lowering sperm quality in old age. Two hundred and one healthy fertile men of three age groups (20-40 years, n=64; 40-60 years, n=61; and >60 years, n=76) were recruited. Expression of CFTR was determined by RT-PCR, western blot, and immunofluorescence staining. Collected sperm were treated with CFTR inhibitor or potentiator. Sperm quality was assessed by motility and bicarbonate-induced capacitation. The results showed that the expression of CFTR on the equatorial segment and neck region of sperm was significantly decreased in an age-dependent manner. Reduction of CFTR expression in sperm from old men was correlated with lowered forward motility and decreased HCO3(-) sensitivity required for sperm capacitation. Activation of CFTR by genistein partially rescued the decreased forward motility in sperm from old men. Decreased CFTR expression in sperm was also found to be associated with lowered sperm quality in aging mice. These results suggest that age-dependent downregulation of CFTR in sperm leads to lowered sperm quality in old age sperm. CFTR may be a pontential target for rescuing sperm motility as well as a fertility indicator in old age men.
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Identification of Ube2b as a novel target of androgen receptor in mouse sertoli cells.
Biol. Reprod.
PUBLISHED: 01-01-2013
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Many genes are regulated by androgen and its receptor (AR), but the direct target genes of AR, especially those involved in spermatogenesis and male infertility, remain unclear. Here, we identified ubiquitin-conjugating enzyme E2B (Ube2b) as a critical target gene of AR. The expression of UBE2B was decreased in the testes of Sertoli cell AR knockout (S-AR(-/y)) mice analyzed by quantitative RT-PCR (qRT-PCR) and immunofluorescence. The upregulation of Ube2b gene by testosterone was further demonstrated by Western blot and qRT-PCR in TM4 cells, a mouse Sertoli cell line. Moreover, luciferase assay, electrophoretic mobility shift assay, and chromatin immunoprecipitation assay validated that the ligand-bound AR activated Ube2b transcription via direct binding to the androgen-responsive element of the Ube2b promoter. In vitro analyses showed that testosterone increased UBE2B expression and activated H2A ubiquitylation, while downregulation of UBE2B blocked the testosterone-induced H2A ubiquitylation. The ubiquitylation of H2A was markedly decreased in the testes of S-AR(-/y) mice by immunohistochemistry. Digital gene expression analysis showed that 113 genes were significantly downregulated and 71 were upregulated by UBE2B in TM4 cells. These results suggest that Ube2b, as a direct AR transcriptional target in Sertoli cells, mediates the function of AR in spermatogenesis by promoting H2A ubiquitylation.
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Increased expression of pregnancy up-regulated non-ubiquitous calmodulin kinase is associated with poor prognosis in clear cell renal cell carcinoma.
PLoS ONE
PUBLISHED: 01-01-2013
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The aims of this study were to evaluate the clinical significance and potential prognostic value of pregnancy up-regulated non-ubiquitous calmodulin kinase (PNCK) in clear cell renal cell carcinoma (ccRCC) patients.
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A genome-wide association study in Chinese men identifies three risk loci for non-obstructive azoospermia.
Nat. Genet.
PUBLISHED: 08-17-2011
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Non-obstructive azoospermia (NOA) is one of the most severe forms of male infertility. Its pathophysiology is largely unknown, and few genetic influences have been defined. To identify common variants contributing to NOA in Han Chinese men, we performed a three-stage genome-wide association study of 2,927 individuals with NOA and 5,734 controls. The combined analyses identified significant (P < 5.0 × 10(-8)) associations between NOA risk and common variants near PRMT6 (rs12097821 at 1p13.3: odds ratio (OR) = 1.25, P = 5.7 × 10(-10)), PEX10 (rs2477686 at 1p36.32: OR = 1.39, P = 5.7 × 10(-12)) and SOX5 (rs10842262 at 12p12.1: OR = 1.23, P = 2.3 × 10(-9)). These findings implicate genetic variants at 1p13.3, 1p36.32 and 12p12.1 in the etiology of NOA in Han Chinese men.
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A novel nonsense mutation in the androgen receptor gene causes the complete androgen insensitivity syndrome.
J. Androl.
PUBLISHED: 07-14-2011
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We identified an unusual novel nonsense mutation in exon 3 of the androgen receptor (AR) gene in a patient with complete androgen insensitivity that was persistence of Wolffian derivatives. Sequence analysis revealed a substitution (C?T) at position 2211 and a deletion of G at position 2213 in exon 3 of the AR gene, resulting in the conversion of arginine(CGG) to a stop codon (TGA) of the AR. Western blotting demonstrated a truncated AR with around 70 kd was expressed. Histology of patients testes showed that seminiferous tubules were totally filled with Sertoli cells without germ cells. Immunohistochemistry revealed positive AR localization in the nuclei of Sertoli cells and epithelia of efferent ductule and vas deferens. AR immunoexpression was stronger in the epithelia of efferent ductule and vas deferens than in Sertoli cells. The study extends the spectrum of exon 3 mutations in the AR gene.
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A systematic analysis on DNA methylation and the expression of both mRNA and microRNA in bladder cancer.
PLoS ONE
PUBLISHED: 07-05-2011
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DNA methylation aberration and microRNA (miRNA) deregulation have been observed in many types of cancers. A systematic study of methylome and transcriptome in bladder urothelial carcinoma has never been reported.
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Frequent mutations of genes encoding ubiquitin-mediated proteolysis pathway components in clear cell renal cell carcinoma.
Nat. Genet.
PUBLISHED: 06-03-2011
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We sequenced whole exomes of ten clear cell renal cell carcinomas (ccRCCs) and performed a screen of ?1,100 genes in 88 additional ccRCCs, from which we discovered 12 previously unidentified genes mutated at elevated frequencies in ccRCC. Notably, we detected frequent mutations in the ubiquitin-mediated proteolysis pathway (UMPP), and alterations in the UMPP were significantly associated with overexpression of HIF1? and HIF2? in the tumors (P = 0.01 and 0.04, respectively). Our findings highlight the potential contribution of UMPP to ccRCC tumorigenesis through the activation of the hypoxia regulatory network.
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Chemical synthesis of bacteriophage G4.
PLoS ONE
PUBLISHED: 05-13-2011
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Due to recent leaps forward in DNA synthesis and sequencing technology, DNA manipulation has been extended to the level of whole-genome synthesis. Bacteriophages occupy a special niche in the micro-organic ecosystem and have potential as a tool for therapeutic agent. The purpose of this study was to carry out chemical synthesis of the bacteriophage G4 and the study of its infectivity.
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Frequent mutations of chromatin remodeling genes in transitional cell carcinoma of the bladder.
Nat. Genet.
PUBLISHED: 05-13-2011
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Transitional cell carcinoma (TCC) is the most common type of bladder cancer. Here we sequenced the exomes of nine individuals with TCC and screened all the somatically mutated genes in a prevalence set of 88 additional individuals with TCC with different tumor stages and grades. In our study, we discovered a variety of genes previously unknown to be mutated in TCC. Notably, we identified genetic aberrations of the chromatin remodeling genes (UTX, MLL-MLL3, CREBBP-EP300, NCOR1, ARID1A and CHD6) in 59% of our 97 subjects with TCC. Of these genes, we showed UTX to be altered substantially more frequently in tumors of low stages and grades, highlighting its potential role in the classification and diagnosis of bladder cancer. Our results provide an overview of the genetic basis of TCC and suggest that aberration of chromatin regulation might be a hallmark of bladder cancer.
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Comparative mRNA and microRNA expression profiling of three genitourinary cancers reveals common hallmarks and cancer-specific molecular events.
PLoS ONE
PUBLISHED: 04-07-2011
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Genome-wide gene expression profile using deep sequencing technologies can drive the discovery of cancer biomarkers and therapeutic targets. Such efforts are often limited to profiling the expression signature of either mRNA or microRNA (miRNA) in a single type of cancer.
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Decreased expression of dual-specificity phosphatase 9 is associated with poor prognosis in clear cell renal cell carcinoma.
BMC Cancer
PUBLISHED: 03-20-2011
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The molecular mechanisms involved in the development and progression of clear cell renal cell carcinomas (ccRCCs) are poorly understood. The objective of this study was to analyze the expression of dual-specificity phosphatase 9 (DUSP-9) and determine its clinical significance in human ccRCCs.
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MicroRNA expression signatures of bladder cancer revealed by deep sequencing.
PLoS ONE
PUBLISHED: 03-02-2011
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MicroRNAs (miRNAs) are a class of small noncoding RNAs that regulate gene expression. They are aberrantly expressed in many types of cancers. In this study, we determined the genome-wide miRNA profiles in bladder urothelial carcinoma by deep sequencing.
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The genomic sequence of the Chinese hamster ovary (CHO)-K1 cell line.
Nat. Biotechnol.
PUBLISHED: 02-23-2011
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Chinese hamster ovary (CHO)-derived cell lines are the preferred host cells for the production of therapeutic proteins. Here we present a draft genomic sequence of the CHO-K1 ancestral cell line. The assembly comprises 2.45 Gb of genomic sequence, with 24,383 predicted genes. We associate most of the assembled scaffolds with 21 chromosomes isolated by microfluidics to identify chromosomal locations of genes. Furthermore, we investigate genes involved in glycosylation, which affect therapeutic protein quality, and viral susceptibility genes, which are relevant to cell engineering and regulatory concerns. Homologs of most human glycosylation-associated genes are present in the CHO-K1 genome, although 141 of these homologs are not expressed under exponential growth conditions. Many important viral entry genes are also present in the genome but not expressed, which may explain the unusual viral resistance property of CHO cell lines. We discuss how the availability of this genome sequence may facilitate genome-scale science for the optimization of biopharmaceutical protein production.
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CD147 is required for matrix metalloproteinases-2 production and germ cell migration during spermatogenesis.
Mol. Hum. Reprod.
PUBLISHED: 02-22-2011
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Spermatogenesis is a highly programmed process that requires the degradation of the extracellular matrix and the remodeling of tight junctions (TJ) to facilitate differentiating germ cell migration. Matrix metalloproteinases (MMPs) are essential in regulating Sertoli cell TJ in the testis. CD147 is known to stimulate the production of MMPs in tumor metastasis and its knockout mice are infertile. However, the functional relationship between CD147 and MMPs in spermatogenesis has not been investigated. In the present study, we examined the expression profile of CD147 and MMPs during mouse testicular development by RT-PCR, western blot and immunofluorescence staining. We also examined CD147 involvement in the production of MMP-2 and the migration of germ cells (GC-1 and GC-2 cells) using CD147 antibody or synthetic microRNA mimics-mediated knockdown. The results showed that CD147 was present at all stages of testicular development from 7 to 56 days post-partum (dpp). CD147 expression was found to increase after 21 days from moderate levels in 7 and 14 days. Of the eight MMPs studied, MMP-2, MMP-7, MMP-9 and MMP-23 were detected to have changes in expression during testicular development, with MMP-2 showing the largest change. CD147 and MMP-2 were co-localized in spermatogonia, spermatocytes and round spermatids in mouse testis, while in human testis, they were co-localized in spermatocytes and round spermatids. MMP-2 expression and migration of GC-1 and GC-2 cells were reduced by interfering with CD147 expression and function in vitro. These data suggest that CD147 regulates migration of spermatogonia and spermatocytes via induction of MMP-2 production during spermatogenesis.
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Epigenetic inactivation of PCDH10 in human prostate cancer cell lines.
Cell Biol. Int.
PUBLISHED: 02-15-2011
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PCDH10 (protocadherin-10), a novel tumour suppressor gene, is down-regulated in several human cancers due to hypermethylation of promoter CGIs (CpG islands). Here, we investigated the expression of PCDH10 in different normal adult tissues and in a panel of prostate cancer cell lines. PCDH10 was widely expressed in normal tissues with higher levels in the prostate. The expression of PCDH10 was markedly reduced or silenced in prostate cancer cell lines compared with normal adult prostate tissue. Decreased PCDH10 expression was correlated with the methylation status of the PCDH10 promoter. Furthermore, the DNA demethylating agent 5-azacytidin restored PCDH10 expression by suppressing PCDH10 promoter methylation in prostate cancer cell lines. Treatment with Trichostatin A alone had no significant effect on the expression of PCDH10 but enhanced the effect of 5-azacytidin. In conclusion, we found that the decreased PCDH10 expression in prostate cancer cells was associated with the aberrant methylation of PCDH10 promoter CGI. Our results may contribute to the understanding of the role of PCDH10 inactivation in the progression of prostate cancers.
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Identification and characterization of human PCDH10 gene promoter.
Gene
PUBLISHED: 01-03-2011
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Recent studies have suggested roles for PCDH10 as a novel tumor suppressor gene. In our previous work, we located the core promoter of PCDH10 to a 462-bp segment of 5-flanking region characterized by a high GC content. Here we further identified and characterized the promoter for PCDH10. Transient transfection of PC3 and LNCaP cells with a series of deleted promoter constructs indicated that the minimal promoter region was between nucleotides -144 and -99. This segment contained a CAAT box, a GT box, and a putative transcription factor binding site for AP-4. Mutational analysis identified that the CAAT box and GT box are necessary for promoter activity. Ectopic expression of NF-Ys increased reporter gene activity, whereas expression of a dominant-negative NF-YA decreased reporter gene activity. Co-transfection of Sp1/Sp3 expression plasmids enhanced reporter gene activity in a dose-dependent manner. Mithramycin A, an inhibitor of Sp-DNA interaction, reduced PCDH10 promoter activity. Electrophoretic mobility shift assays and chromatin immunoprecipitation demonstrated binding of transcription factors Sp1/Sp3 to the promoter region in vitro and in vivo. Our data show that Sp1/Sp3 and CBF/NF-Y transcription factors play a crucial role in the basal expression of the human PCDH10 gene.
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Functional expression of ropporin in human testis and ejaculated spermatozoa.
J. Androl.
PUBLISHED: 08-12-2010
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Asthenozoospermia is a common cause of human male infertility, but the molecular mechanism is not fully understood. With Affymetrix Genechips, ropporin, a component of sperm flagella, was identified by comparing the expression profiles in ejaculated spermatozoa from normozoospermic men and patients with asthenozoospermia. Immunohistochemistry was used to analyze the expression characteristic of ropporin in human testis. Reverse transcription-polymerase chain reaction, Western blotting, and indirect immunofluorescence assay were used to determine the expression of ropporin in ejaculated spermatozoa from normozoospermic and asthenozoospermic men. The results showed that ropporin was predominantly expressed in round spermatids in human testis, and located in the principal piece and the end piece of spermatozoa flagella. The expression level of ropporin was significantly lower in asthenozoospermic men than in normozoospermic controls. These data suggested that ropporin may be involved in sperm motility and its decreased expression may contribute to the low sperm motility in asthenozoospermic patients.
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Integrated profiling of microRNAs and mRNAs: microRNAs located on Xq27.3 associate with clear cell renal cell carcinoma.
PLoS ONE
PUBLISHED: 08-04-2010
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With the advent of second-generation sequencing, the expression of gene transcripts can be digitally measured with high accuracy. The purpose of this study was to systematically profile the expression of both mRNA and miRNA genes in clear cell renal cell carcinoma (ccRCC) using massively parallel sequencing technology.
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UPK3A: a promising novel urinary marker for the detection of bladder cancer.
Urology
PUBLISHED: 03-25-2010
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Current methods for reliable detection of bladder cancer have some limitations. Finding better noninvasive methods for detection of bladder cancer is an important topic in urology. We want to evaluate prospectively the early detection power of human uroplakin 3 A (UPK3A) for bladder cancer.
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Rat bone marrow derived mesenchymal progenitor cells support mouse ES cell growth and germ-like cell differentiation.
Cell Biol. Int.
PUBLISHED: 04-23-2009
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Mouse embryonic fibroblasts (MEFs) have been used as feeder cells to support the growth of mouse embryonic stem cell (mESC) and primordial germ cells (PGC) in culture for many years. However, MEF preparation is a complex and tedious task. Recently, there are reports indicating that the microenvironment provided by bone marrow stromal cells could support the survival of embryonic-like stem cells in bone marrow. In this report, rat bone marrow derived mesenchymal progenitor cells (MPC) were used as feeder cells to culture mouse Oct4-GFP ES cell and ES cell derived germ cells. FACS results show that similar to MEF, rat MPC could efficiently support growth of the mouse Oct4-GFP ES cell line in culture (MPC 85.5 +/- 5.1% vs MEF 84.1 +/- 6.2%). ES cells could be subcultured for >15 passages without losing morphological characteristics. The cultured cells expressed stem cell marker alkaline phosphatase, Oct4, Sox2, and SSEA-1. Furthermore, rat MPC cells were able to support survival of germ cells isolated from mouse Oct4-GFP ES cell formed embryoid bodies (EB). After induction by retinoic acid for 7 days, some isolated cells differentiated to spermatogonial stem-like cells, expressing Mvh, Stra-8, Hsp90-a, integrinb1 and a6. Compared with traditional MEF culture systems, the rat MPC culture system is effective in supporting ES cell growth and is easy to prepare.
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Developmental expression pattern of a novel gene, TSG23/Tsg23, suggests a role in spermatogenesis.
Mol. Hum. Reprod.
PUBLISHED: 02-24-2009
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A novel gene, TSG23/Tsg23, was identified by comparing the expression profiles of human adult and fetal testis using Affymetrix Genechips. RT-PCR analysis from multiple human and mouse tissues indicated TSG23/Tsg23 mRNA was mainly expressed in the testis. In situ hybridization revealed that TSG23/Tsg23 mRNA was located in spermatocytes and round spermatids of the seminiferous tubules in human and mouse testis. To further confirm the result from RT-PCR, the antibody for human TSG23 was generated against the protein encoded by the gene. Western blot analysis demonstrated that TSG23 was mainly expressed in human testis, with a molecular weight of about 23 kDa. Immunohistochemistry showed that TSG23 was predominantly located in spermatocytes and round spermatids, consistent with the results from in situ hybridization. In order to explore the function of TSG23 in spermatogenesis, the study compared the expression of TSG23 in the testis from fertile persons and from patients with azoospermia. The results showed that there was less expression in patients with obstructive azoospermia compared with fertile persons, and no detectable TSG23 at mRNA and protein levels in patients with non-obstructive azoospermia. The expression of Tsg23 mRNA was considerably decreased in a time-dependent manner in the testis of an azoospermic mouse model induced by Busulfan. These data suggest that TSG23/Tsg23 is involved in human and mouse spermatogenesis.
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Expression profile of a novel germ cell-specific gene, TSCPA, in mice and human.
J. Huazhong Univ. Sci. Technol. Med. Sci.
PUBLISHED: 01-05-2009
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In order to identify novel genes involved in spermatogenesis, testis cDNA samples from Balb/C mice of different postnatal days were hybridized with the whole mouse genome Affymetrix chip to screen the testis-specific genes. The characteristics of the selected genes were analyzed by RT-PCR as well as other bioinformatic tools. A novel differentially expressed testis-specific gene (GenBank Accession No: NM_029042) in the developmental stages of testes was identified, and named TSCPA. Cellular mapping prediction of TSCPA indicated that its protein was probably expressed in nuclei, and one putative domain (aa 332-377) was anchoring domain of cAMP-dependent type II PK. The result of subcellular localization of GFP-TSCPA fusion protein in Cos-7 cells showed that TSCPA protein was expressed in nuclei. RT-PCR analysis revealed that TSCPA was expressed specifically in mouse and human testis. TSCPA gene was expressed weakly in 21-day-old mouse testis and the expression was increased gradually from 38th day to 6th month of mouse testes. No expression of hTSCPA was found in cryptorchidism and Sertoli-cell-only syndrome patients. It was concluded that the expression profile of TSCPA in human and mice indicated that TSCPA might play an important role in spermatogenesis.
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Synthetic miRNA-mowers targeting miR-183-96-182 cluster or miR-210 inhibit growth and migration and induce apoptosis in bladder cancer cells.
PLoS ONE
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MicroRNAs (miRNAs) function as endogenous regulators of biological behaviors of human cancers. Several natural non-coding RNAs are reported to inhibit miRNAs by base-pairing interactions. These phenomena raise questions about the ability of artificial device to regulate miRNAs. The purpose of this study is to create synthetic devices that target a single miRNA or a miRNA cluster and to ascertain their therapeutic effects on the phenotypes of bladder cancer cells.
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[Association of miR-199a expression with clinicopathologic characteristics and prognosis of renal cell carcinoma].
Nan Fang Yi Ke Da Xue Xue Bao
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To investigate the association of miR-199a expression with the clinicopathologic characteristics and the survival of patients with renal cell carcinoma (RCC).
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Inducing cell proliferation inhibition, apoptosis, and motility reduction by silencing long noncoding ribonucleic acid metastasis-associated lung adenocarcinoma transcript 1 in urothelial carcinoma of the bladder.
Urology
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To study the expression patterns of long noncoding ribonucleic acid (RNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) and the cell proliferation inhibition, apoptosis, and motility changes induced by silencing MALAT1 in urothelial carcinoma of the bladder.
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A dominant-negative mutation of HSF2 associated with idiopathic azoospermia.
Hum. Genet.
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Idiopathic azoospermia (IA) is a severe form of male infertility due to unknown causes. The HSF2 gene, encoding the heat shock transcription factor 2, had been suggested to play a significant role in the spermatogenesis process since the Hsf2-knockout male mice showed spermatogenesis defects. To examine whether HSF2 is involved in the pathogenesis of IA in human, we sequenced all the exons of HSF2 in 766 patients diagnosed with IA and 521 proven fertile men. A number of coding mutations private to the patient group, which include three synonymous mutations and five missense mutations, were identified. Of the missense mutations, our functional assay demonstrated that one heterozygous mutation, R502H, caused a complete loss of HSF2 function and that the mutant suppressed the normal function of the wild-type (WT) allele through a dominant-negative effect, thus leading to the dominant penetrance of the mutant allele. These results support a role for HSF2 in the pathogenesis of IA and further implicate this transcription factor as a potential therapeutic target.
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Long intergenic non-coding RNA TUG1 is overexpressed in urothelial carcinoma of the bladder.
J Surg Oncol
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Long intergenic non-coding RNAs (lincRNAs) are a class of non-coding RNAs that regulate gene expression via chromatin reprogramming. Taurine Up-regulated Gene 1 (TUG1) is a lincRNA that is associated with chromatin-modifying complexes and plays roles in gene regulation. In this study, we determined the expression patterns of TUG1 and the cell proliferation inhibition and apoptosis induced by silencing TUG1 in urothelial carcinoma of the bladder.
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Developmental expression and function of DKKL1/Dkkl1 in humans and mice.
Reprod. Biol. Endocrinol.
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Experiments were designed to identify the developmental expression and function of the Dickkopf-Like1 (DKKL1/Dkkl1) gene in humans and mice.
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Whole-genome synthesis and characterization of viable S13-like bacteriophages.
PLoS ONE
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Unprecedented progresses in high-throughput DNA sequencing and de novo gene synthesis technologies have allowed us to create living organisms in the absence of natural template.
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Inducing cell proliferation inhibition and apoptosis via silencing Dicer, Drosha, and Exportin 5 in urothelial carcinoma of the bladder.
J Surg Oncol
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MicroRNAs (miRNAs) are aberrantly expressed in cancers. Dicer, Drosha, and Exportin 5 are essential for miRNA processing. In this study, the expression patterns of Dicer, Drosha, and Exportin 5 and the cell proliferation inhibition and apoptosis induced by silencing these genes in urothelial carcinoma of the bladder were determined.
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Ketamine-associated urinary tract dysfunction: an underrecognized clinical entity.
Urol. Int.
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The use of ketamine as a recreational drug is on the increase among young adults attending clubs and parties. Recreational ketamine users have anecdotally reported increased lower urinary tract symptoms while using the substance.
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CD147 regulates apoptosis in mouse spermatocytes but not spermatogonia.
Hum. Reprod.
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Spermatogenesis is maintained by a dynamic balance between germ cell proliferation and apoptosis. Previous study has demonstrated that CD147 knockout mice are infertile with arrested germ cells. However, the question of whether and how CD147 may be involved in the apoptotic process during spermatogenesis remains elusive. The aim of this study was to evaluate the role of CD147 in the regulation of germ cell apoptosis in mice.
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Single-cell exome sequencing reveals single-nucleotide mutation characteristics of a kidney tumor.
Cell
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Clear cell renal cell carcinoma (ccRCC) is the most common kidney cancer and has very few mutations that are shared between different patients. To better understand the intratumoral genetics underlying mutations of ccRCC, we carried out single-cell exome sequencing on a ccRCC tumor and its adjacent kidney tissue. Our data indicate that this tumor was unlikely to have resulted from mutations in VHL and PBRM1. Quantitative population genetic analysis indicates that the tumor did not contain any significant clonal subpopulations and also showed that mutations that had different allele frequencies within the population also had different mutation spectrums. Analyses of these data allowed us to delineate a detailed intratumoral genetic landscape at a single-cell level. Our pilot study demonstrates that ccRCC may be more genetically complex than previously thought and provides information that can lead to new ways to investigate individual tumors, with the aim of developing more effective cellular targeted therapies.
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Ascorbate antagonizes nickel ion to regulate JMJD1A expression in kidney cancer cells.
Acta Biochim. Biophys. Sin. (Shanghai)
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Abnormal expression of histone demethylase Jumonji domain-containing protein 1A (JMJD1A) is associated with many kinds of cancers. JMJD1A is also a hypoxic response gene and its expression is regulated by hypoxia-inducible factor-1? (HIF-1?). In this study, we determined the role of JMJD1A in development and hypoxia pathway. We also measured the expression of JMJD1A and two hypoxia factors glucose transporter 1 (GLUT1) and vascular endothelial growth factor (VEGF) in 786-0 and HEK293 cells treated with different concentrations of NiCl(2) (2.5-100 ?M) for 24 h, and found that JMJD1A mRNA and protein were up-regulated with increased concentrations of NiCl(2). We then observed that ascorbate could retard the up-regulated effect of NiCl(2)-induced JMJD1A expression in a dose-dependent manner through decreasing the stability of HIF-1? protein. Immunohistochemical analysis further demonstrated ascorbate antagonized Ni(2+)-induced up-regulation of JMJD1A expression in 786-0, HEK293, and OS-RC-2 cells. These findings suggest that both Ni(2+) and ascorbate can regulate the expression of histone demethylase JMJD1A, which is important for cancer development or inhibition.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.