Department of Urology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin Second Road, Shanghai 200025, China.
Department of Urology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin Second Road, Shanghai 200025, China.
Cell Signal. 2023 Oct;110:110836. doi: 10.1016/j.cellsig.2023.110836. Epub 2023 Aug 1.
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.
微小 RNA（miRNA）在癌症的发生和发展中起着关键作用，miR-30c-5p 的失调已在各种恶性肿瘤中观察到，但在膀胱癌（BCa）中尚未进行研究。本研究旨在探讨 miR-30c-5p 在 BCa 中的下调及其机制和预后意义。
采用生物信息学分析和临床标本研究 miR-30c-5p 与 BCa 患者临床信息之间的关系。通过实时 PCR 和 Western blot 评估 miR-30c-5p 及其靶基因的表达水平。通过集落形成能力、CCK-8 和 EdU 测定评估细胞活力。通过流式细胞术测定细胞周期分布和细胞凋亡。还在动物模型中验证了 miR-30c-5p 的抗肿瘤作用。
miR-30c-5p 的表达水平在膀胱肿瘤组织和 BCa 细胞系中均显著降低。低 miR-30c-5p 表达与不良的 TNM 分期和预后不良相关。过表达 miR-30c-5p 观察到抑制 BCa 细胞生长、迁移和侵袭能力，并导致细胞周期停滞。机制上，miR-30c-5p 直接结合并抑制 PRC1，从而阻断 BCa 中的 CDK1/Cyclin B1 轴，从而损害 BCa 细胞活力并诱导细胞周期停滞在 G2/M 期。
下调的 miR-30c-5p 通过其靶基因 PRC1 促进 BCa，miR-30c-5p 是预测 BCa 患者临床结局的有利生物标志物，具有成为治疗靶点的潜力。
