avoiding-ischemia-reperfusion-injury-in-liver-transplantation

Avoiding Ischemia Reperfusion Injury in Liver Transplantation

Currently, ex situ machine perfusion is a burgeoning technique that provides a better preservation method for donor organs than conventional static cold ...

Guangdong Academy of Medical Sciences

Vascular invasion, rather than tumor size, was applied into the 7th edition of the AJCC TNM staging system to predict survival of solitary hepatocellular carcinoma (HCC) patients. However, does this mean tumor size is of little value in prognostic prediction? The current study was designed to explore the prognostic ability of tumor sizes in solitary HCC.

The power of tumor sizes in predicting the survival of solitary hepatocellular carcinoma patients.

MicroRNAs (miRNAs) play a pivotal role in hepatocellular carcinoma (HCC) progression and have been confirmed to participate in the carcinogenesis and development of HCC. However, the relationship between miR-497-5p and HCC remains unclear.

lncRNA XIST regulates proliferation and migration of hepatocellular carcinoma cells by acting as miR-497-5p molecular sponge and targeting PDCD4.

Non-SMC condensing I complex subunit H (NCAPH) is a member of the Barr protein family and part of the condensin I complex. The upregulation of NCAPH is associated with poor prognosis in patients with colon cancer. However, the relationship between NCAPH and hepatocellular carcinoma (HCC) remains unclear. This study aimed to explore NCAPH expression in HCC tissues and to investigate NCAPH functions in HCC cells. In this study, we found that high expression of NCAPH in HCC indicated worse prognosis via bioinformatics analysis. Consistently, quantitative real-time polymerase chain reaction assays in 20 pairs of HCC specimens and the immunohistochemical analysis of 100 HCC tissues showed the upregulation of NCAPH. We established stable NCAPH-overexpressing and NCAPH knockdown cell lines. Cell Counting Kit-8 assays and colony formation assay were performed to analyze cell proliferation. Migration and invasion were analyzed by Transwell assays. Subcutaneous xenograft models were used to explore the role of NCAPH in tumor formation in vivo. Our results showed that NCAPH promoted tumor proliferation, migration, and invasion in vitro and in vivo. In conclusion, our findings indicate that NCAPH could serve as a novel prognostic biomarker and a potential therapeutic target for patients with HCC.

Non-SMC condensin I complex subunit H enhances proliferation, migration, and invasion of hepatocellular carcinoma.

Hepatitis B virus (HBV) infection is a global health problem and interferon-alpha (IFN-α) is one of the effective therapies. However, little is known about the genetic background of the HBV infection or the genetic determinants of the IFN-α treatment response. Thus, we aim to explore the possible molecular mechanisms of HBV infection and its response to the IFN-α therapy with a comprehensive bioinformatics analysis.

Bioinformatics analysis on multiple Gene Expression Omnibus datasets of the hepatitis B virus infection and its response to the interferon-alpha therapy.

Obg-like ATPase 1 (OLA1) has been found to have a dual role in cancers. However, the relationship between OLA1 and hepatocellular carcinoma (HCC) remains unclear.

Obg-like ATPase 1 (OLA1) overexpression predicts poor prognosis and promotes tumor progression by regulating P21/CDK2 in hepatocellular carcinoma.

N-methyladenosine (m6A) RNA methylation contributes to the cancer stem cell (CSC) phenotype through regulating gene expression. YTHDF2, an m6A reader, was shown to be associated with hepatocellular carcinoma (HCC) patient prognosis. However, the effect of YTHDF2 on liver CSC and cancer metastasis and the molecular mechanism of this effect have not been documented. Here, we show that YTHDF2 expression is negatively correlated with HCC patient survival in both data from the Cancer Genome Atlas (TCGA) database and clinical data from our center. By detecting CD133 cells and carrying out sphere culture assays, we found that knockdown of YTHDF2 led to impaired stemness in Hep3B and Huh7 cells. In contrast, overexpression of YTHDF2 increased the CSC phenotype. Mechanistically, the knockdown and overexpression of YTHDF2 in liver cancer cells resulted in decreased and increased m6A levels in the 5'-untranslated region (UTR) of OCT4 mRNA, respectively, leading to decreased and increased OCT4 protein expression, respectively. A luciferase activity assay showed that mutation of the corresponding m6A methylation sequence in the 5'-UTR of OCT4 mRNA caused significantly decreased gene expression, suggesting a role for YTHDF2-dependent m6A methylation in protein translation. Polysome profiling results also indicated the knockdown and overexpression of YTHDF2 could decrease and increase OCT4 translation, respectively. In particular, overexpression of OCT4 rescued the impaired stemness caused by YTHDF2 depletion, which confirmed the effect of YTHDF2 on CSC phenotype is dependent on OCT4. In vivo, the loss of YTHDF2 reduced tumor burden and inhibited lung metastasis following orthotopic transplantation in nude mice. Last, we demonstrated that YTHDF2 expression is positively correlated with OCT4 expression and m6A levels in the 5'-UTR of OCT4 mRNA in clinical HCC specimens. In conclusion, YTHDF2 promotes the CSC liver phenotype and cancer metastasis by modulating the m6A methylation of OCT4 mRNA.

YTHDF2 promotes the liver cancer stem cell phenotype and cancer metastasis by regulating OCT4 expression via m6A RNA methylation.

In this study, we investigated the mechanistic role of the long non-coding RNA (lncRNA) AC092171.4 in hepatocellular carcinoma (HCC). AC092171.4 was significantly upregulated in HCC tumor tissues compared to normal liver tissues. HCC patients with high AC092171.4 expression showed poorer overall survival (OS) and disease-free survival (DFS) than those with low AC092171.4 expression.  cell proliferation, migration and invasiveness were all higher in AC092171.4-overexpressing HCC cells, but lower in AC092171.4-silenced HCC cells, than in controls. Balb/c nude mice injected with AC092171.4-silenced HCC cells had smaller xenograft tumors, which showed less growth and pulmonary metastasis than control tumors. Bioinformatics analyses and dual luciferase reporter assays confirmed that AC092171.4 binds directly to miR-1271, which targets the 3'UTR of GRB2 mRNA. AC092171.4 expression correlates negatively with miR1271 expression and correlates positively with GRB2 mRNA expression in HCC tissues from patients. HCC cells co-transfected with miR-1271 mimics and sh-AC092171.4 show less proliferation, migration, invasiveness, GRB2 protein, and epithelial to mesencyhmal transition (EMT) than sh-AC092171.4-transfected HCC cells. These findings demonstrate that AC092171.4 promotes growth and progression of HCC by sponging miR-1271 and upregulating GRB2. This makes AC092171.4 a potential prognostic indicator and therapeutic target for HCC patients.

Long noncoding RNA AC092171.4 promotes hepatocellular carcinoma progression by sponging microRNA-1271 and upregulating GRB2.

The number of pediatric deceased organ donors has recently declined, and the nonutilization of pediatric liver allografts has limited the development of liver transplantation. We determined the utilization rate of pediatric livers and identified risk factors for graft discard.

Deceased Donor Predictors for Pediatric Liver Allograft Utilization.

Pancreatic cancer (PC) is one of the most common cancers and the leading cause of cancer-related death worldwide. Exploring novel predictive biomarkers for PC patients' prognosis is in urgent need.

A four prognosis-associated lncRNAs (PALnc) based risk score system reflects immune cell infiltration and predicts patient survival in pancreatic cancer.

Integrin β (ITGB) superfamily members have been reported to play important roles in multiple biological functions in various cancers. However, the prognostic and oncologic values of ITGB superfamily members have not been systematically investigated in pancreatic cancer (PC). In this study, the mRNA expression and biological functions of ITGB superfamily members in PC were evaluated by bioinformatic analysis. Our results demonstrated that ITGB1, ITGB4, ITGB5 and ITGB6 overexpressions were significantly associated with advanced AJCC stage and histologic grade, and worse prognosis in PC. A prognostic signature based on ITGB1, ITGB4, ITGB5 and ITGB6 showed a reliable predictive performance. Furthermore, one CpGs (cg20545410) in promoter region of ITGB1, four (cg18709893, cg15700850, cg20667796 and cg18326022) of ITGB4, two (cg10977398 and cg03518058) of ITGB5 and one (cg23008083) of ITGB6 were negatively associated with their corresponding mRNA expression, and positively associated with prognosis in PC. We also identified TFAP2A as the potential transcription factor for ITGB4, SP1 for ITGB1 and ITGB6, and FHL2 for ITGB5 and ITGB6. ITGB1, ITGB4, ITGB5 and ITGB6 overexpressions were all significantly involved in focal adhesion signalling pathway. ITGB1 and ITGB5 overexpressions also associated with up-regulation of TGF-β and WNT signalling pathway, whereas ITGB4 and ITGB6 overexpressions associated with up-regulation of Notch signalling pathway. Besides, ITGB1, ITGB5 and ITGB6 overexpressions significantly correlated with immunosuppression in PC. In summary, our study investigated the multilevel prognostic and biological values of ITGB superfamily members in PC.

Characterization of the prognostic and oncologic values of ITGB superfamily members in pancreatic cancer.

Hepatocellular carcinoma (HCC) is one of the most commonly diagnosed digestive cancers and the fourth leading cause of death worldwide. Long noncoding RNAs (lncRNAs) with key roles in HCC development and progression have emerged and are used in the diagnosis and prognostic prediction of HCC. The lncRNA gradually increased during hepatocarcinogenesis () is a novel lncRNA with aberrant expression in many tumors, but its prognostic value and biological role in HCC have not been fully studied. Thus, the aim of this study was to explore the expression pattern and potential biological role of  in HCC.

Article	Year
The power of tumor sizes in predicting the survival of solitary hepatocellular carcinoma patients. Cancer medicine\| PubMed ID: 30430769	2018
lncRNA XIST regulates proliferation and migration of hepatocellular carcinoma cells by acting as miR-497-5p molecular sponge and targeting PDCD4. Cancer cell international\| PubMed ID: 31384173	2019
Non-SMC condensin I complex subunit H enhances proliferation, migration, and invasion of hepatocellular carcinoma. Molecular carcinogenesis\| PubMed ID: 31523845	2019
Bioinformatics analysis on multiple Gene Expression Omnibus datasets of the hepatitis B virus infection and its response to the interferon-alpha therapy. BMC infectious diseases\| PubMed ID: 31996147	2020
Obg-like ATPase 1 (OLA1) overexpression predicts poor prognosis and promotes tumor progression by regulating P21/CDK2 in hepatocellular carcinoma. Aging\| PubMed ID: 32045367	2020
YTHDF2 promotes the liver cancer stem cell phenotype and cancer metastasis by regulating OCT4 expression via m6A RNA methylation. Oncogene\| PubMed ID: 32366907	2020
Long noncoding RNA AC092171.4 promotes hepatocellular carcinoma progression by sponging microRNA-1271 and upregulating GRB2. Aging\| PubMed ID: 32692718	2020
Deceased Donor Predictors for Pediatric Liver Allograft Utilization. Transplantation proceedings\| PubMed ID: 32718748	2020
A four prognosis-associated lncRNAs (PALnc) based risk score system reflects immune cell infiltration and predicts patient survival in pancreatic cancer. Cancer cell international\| PubMed ID: 33061845	2020
Characterization of the prognostic and oncologic values of ITGB superfamily members in pancreatic cancer. Journal of cellular and molecular medicine\| PubMed ID: 33073486	2020
Overexpression of is Associated with a Poor Prognosis and Immune Infiltration in Hepatocellular Carcinoma. OncoTargets and therapy\| PubMed ID: 33209037	2020

Shanzhou Huang

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