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

细胞周期蛋白依赖激酶1 阻塞(统计) 细胞周期 癌症研究 小RNA 细胞周期蛋白B1 癌症 医学 生物 内科学 基因 计算机科学 遗传学 计算机网络
作者
Yining Hao,Yu Zhu,Fukang Sun,Danfeng Xu,Chenghe Wang
出处
期刊:Cellular Signalling [Elsevier BV]
卷期号:110: 110836-110836 被引量:11
标识
DOI:10.1016/j.cellsig.2023.110836
摘要

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. 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. 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. 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.
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