MicroRNA-30c-5p arrests bladder cancer G2/M phase and suppresses its progression by targeting PRC1-mediated blocking of CDK1/Cyclin B1 axis.

Abstract

BACKGROUND:

MicroRNAs (miRNAs) play a critical role in cancer development and progression, the dis-regulation of miR-30c-5p has been observed in various malignant tumors but no research was done in bladder cancer (BCa). This study aims to investigate the downregulation of miR-30c-5p in BCa, and examine its mechanism and prognostic significance.

METHODS:

Bioinformatics analyses and clinical specimens were employed to investigate the relationship between miR-30c-5p and clinical information in BCa patients. The expression levels of miR-30c-5p and its target gene were assessed by real-time PCR and western blot. Cell viability was evaluated through clonogenic capacity, CCK-8, and EdU assays. Cell cycle distribution and cell apoptosis were determined by flow cytometry. The anti-tumor effect of miR-30c-5p was also validated in animal models.

RESULTS:

The expression levels of miR-30c-5p were significantly decreased in both bladder tumor tissue and BCa cell lines. Low miR-30c-5p expression was found to be correlated with unfavorable TNM stages and poor prognosis. Over-expressing miR-30c-5p was observed to hinder BCa cell growth, migration, and invasion abilities and causing cell cycle arrest. Mechanistically, miR-30c-5p directly binds and suppresses PRC1, thereby blocking the CDK1/Cyclin B1 axis in BCa, thus impairing BCa cell viability and inducing cell cycle arrest at G2/M phase.

CONCLUSION:

Down-regulated miR-30c-5p promotes BCa through its target gene PRC1, miR-30c-5p is a favorable biomarker for predicting clinical outcomes in BCa patients and has the potential to be a therapeutic target.

• Authors: Yining Hao, Yu Zhu, Fukang Sun, Danfeng Xu, Chenghe Wang
• Journal: Cellular signalling (Cell Signal) Vol. 110 Pg. 110836 (10 2023) ISSN: 1873-3913 [Electronic] England
• PMID: 37532136 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2023. Published by Elsevier Inc.

Chemical References

• Cyclin B1
• MicroRNAs
• MIRN30C2 microRNA, human
• CDK1 protein, human
• CCNB1 protein, human

Topics

• Animals
• Cell Division
• Cell Line, Tumor
• Cell Proliferation (genetics)
• Cyclin B1 (genetics, metabolism)
• Gene Expression Regulation, Neoplastic
• MicroRNAs (genetics, metabolism)
• Urinary Bladder Neoplasms (genetics, pathology)
• Humans