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Transmesenteric Laparoscopic Pyeloplasty in Trendelenburg Position for Horseshoe Kidney with Hydronephrosis

Due to anomalous anatomy, pyeloplasty with a horseshoe kidney (HSK) presents a technical challenge. Previously, we reported a technique of intraperitoneal ...

Shenzhen university

About 10-20% of patients with bladder cancer (BC) progress to muscle-invasive diseases, of which the underlying key molecular events have yet to be addressed.

PABPN1 regulates mRNA alternative polyadenylation to inhibit bladder cancer progression.

Alternative polyadenylation (APA) is emerging as a major posttranscriptional mechanism for gene regulation in cancer. A prevailing hypothesis is that shortening of the 3' untranslated region (3'UTR) increases oncoprotein expression because of the loss of miRNA-binding sites (MBSs). We showed that the longer 3'UTR is associated with a more advanced tumor stage in patients with clear cell renal cell carcinoma (ccRCC). More surprisingly, 3'UTR shortening is correlated with better overall survival in patients with ccRCC. Furthermore, we identified a mechanism by which longer transcripts lead to increased oncogenic protein and decreased tumor-suppressive protein expression compared to the shorter transcripts. In our model, shortening of 3'UTRs by APA may increase the mRNA stability of the majority of the potential tumor-suppressor genes due to the loss of MBSs and AU-rich elements (AREs). Unlike potential tumor-suppressor genes, the potential oncogenes display much lower MBS and ARE density and globally much higher m6A density in distal 3'UTRs. As a result, 3'UTRs shortening decreases the mRNA stability of potential oncogenes and enhances the mRNA stability of potential tumor-suppressor genes. Our findings highlight the cancer-specific pattern of APA regulation and extend our understanding of the mechanism of APA-mediated 3'UTR length changes in cancer biology.

Lengthening of 3' Untranslated Regions of mRNAs by Alternative Polyadenylation Is Associated With Tumor Progression and Poor Prognosis of Clear Cell Renal Cell Carcinoma.

Clear cell renal cell carcinoma (ccRCC) is the most common renal cancer. Alternative polyadenylation (APA) plays an important role in the progression and immunity of multiple tumors. Although immunotherapy has emerged as an important treatment option for metastatic renal cell carcinoma, whether APA affects the tumor immune microenvironment (TIME) in ccRCC remains unclear.

Comprehensive analysis of alternative polyadenylation regulators of CTLA4 and immune infiltration in clear cell renal cell carcinoma.

Alternative polyadenylation (APA) is an important post-transcriptional regulatory mechanism in cancer development and progression. Poly(A) binding protein nuclear 1 (PABPN1) is a gene that encodes abundant nuclear protein, binds with high affinity to nascent poly(A) tails, and is crucial for 3'-UTR (3'-untranslated region) APA. Although PABPN1 has been recently reported as a dominant master APA regulator in clear cell renal cell carcinoma (ccRCC), the underlying functional mechanism remain unclear and the genes subject to PABPN1 regulation that contribute to ccRCC progression have not been identified. Here, we found that PABPN1 is upregulated in ccRCC, and its expression is highly associated with the clinical prognosis of ccRCC patients. PABPN1 promotes ccRCC cell proliferation, migration, invasion, and exerts an influence on sphingolipid metabolism and cell cycle. Moreover, PABPN1 depletion significantly suppressed cancer cell growth via induction of cell cycle arrest and apoptosis. In particular, we characterized PABPN1-regulated 3'-UTR APA of sphingosine-1-phosphate lyase 1 (SGPL1) and cellular repressor of E1A stimulated genes 1 (CREG1), which contribute to ccRCC progression. Collectively, our data revealed that PABPN1 promotes ccRCC progression at least in part, by suppressing SGPL1 and CREG1. Thus, PABPN1 may be a potential therapeutic target in ccRCC.

PABPN1 promotes clear cell renal cell carcinoma progression by suppressing the alternative polyadenylation of SGPL1 and CREG1.

Technique modifications that aim to improve ergonomics of the surgical procedure without repositioning the upper tract urothelial carcinoma patients remain a challenge to urologists. We offer a novel technique to perform intraperitoneal laparoscopic single-site radical nephroureterectomy and pelvic lymph nodes dissection/retroperitoneal lymph nodes dissection in a supine position. Our novel technique is feasible and offers a significant improvement in operative efficiency, particularly in patients with locally advanced disease.

Intraperitoneal laparoscopic single-site lymph node dissection in modified supine position during laparoscopic radical nephroureterectomy.

To evaluate the safety and feasibility of intraperitoneal laparoscopic surgery in Trendelenburg position (ILSTP) for pyelolithotomy, pyeloplasty, and heminephrectomy in patients with horseshoe kidneys (HSKs).

Intraperitoneal laparoscopic technique in trendelenburg position: an effective surgical method for pyelolithotomy, pyeloplasty, and heminephrectomy in patients with horseshoe kidneys.

Zinner syndrome (ZS) is a rare anomaly of the Wolffian duct. Here, we present a case of seminal vesiculectomy and ipsilateral nephroureterectomy using laparoscopic surgery in a modified supine position, which was performed in a 30-year-old male patient with ZS. To our knowledge, this is the first report to describe the feasible use of this approach to remove the seminal vesicle and ipsilateral atrophic kidney in a single session.

Article	Year
PABPN1 regulates mRNA alternative polyadenylation to inhibit bladder cancer progression. Cell & bioscience\| PubMed ID: 36879298	2023
Lengthening of 3' Untranslated Regions of mRNAs by Alternative Polyadenylation Is Associated With Tumor Progression and Poor Prognosis of Clear Cell Renal Cell Carcinoma. Laboratory investigation; a journal of technical methods and pathology\| PubMed ID: 36889542	2023
Comprehensive analysis of alternative polyadenylation regulators of CTLA4 and immune infiltration in clear cell renal cell carcinoma. Translational andrology and urology\| PubMed ID: 37181233	2023
PABPN1 promotes clear cell renal cell carcinoma progression by suppressing the alternative polyadenylation of SGPL1 and CREG1. Carcinogenesis\| PubMed ID: 37452741	2023
Intraperitoneal laparoscopic single-site lymph node dissection in modified supine position during laparoscopic radical nephroureterectomy. Journal of surgical case reports\| PubMed ID: 38840897	2024
Intraperitoneal laparoscopic technique in trendelenburg position: an effective surgical method for pyelolithotomy, pyeloplasty, and heminephrectomy in patients with horseshoe kidneys. BMC urology\| PubMed ID: 39468533	2024
Intraperitoneal Laparoscopic Seminal Vesiculectomy and Ipsilateral Nephroureterectomy in Modified Supine Position for Treatment of Zinner's Syndrome. Asian journal of endoscopic surgery\| PubMed ID: 40302168	2025

Ming Xiong

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