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

被引:10
作者
Hao, Yining [1 ]
Zhu, Yu [1 ]
Sun, Fukang [1 ]
Xu, Danfeng [1 ]
Wang, Chenghe [1 ]
机构
[1] Shanghai Jiao Tong Univ, Ruijin Hosp, Dept Urol, Sch Med, 197 Ruijin Second Rd, Shanghai 200025, Peoples R China
基金
中国国家自然科学基金;
关键词
miRNA; Cell cycle; Bladder cancer; PRC1; MIR-30A/C-5P; RESISTANCE; EXPRESSION; INVASION;
D O I
10.1016/j.cellsig.2023.110836
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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, CCK8, 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.
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页数:11
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