The role of exosomal miR‐375‐3p: A potential suppressor in bladder cancer via the Wnt/β‐catenin pathway
Qi Li, Ting Huyan, Suna Cai, Qiuping Huang, Mengzhao Zhang, Hourong Peng, Yujun Zhang, Ningjing Liu, Wei Zhang
Abstract
miR-375-3p is a significantly downregulated miRNA in bladder cancer (BC). However, its role in BC regulation is still unclear. In this study, we reported that miR-375-3p overexpression inhibited proliferation and migration and promoted apoptosis in BC cells. Frizzled-8 (FZD8) gene is identified as the direct miR-375-3p targeting gene. miR-375-3p blocks the Wnt/β-catenin pathway and downstream molecules Cyclin D1 and c-Myc by inhibiting the expression of FZD8 directly, it could increase caspase 1 and caspase 3 expression and promote T24 cell apoptosis as well. miR-375-3p also showed a significant inhibitory effect in vivo in bladder tumor-bearing nude mice, as demonstrated by the reduced tumor volume and Ki67 proliferation index in tumor tissue. Collectively, miR-375-3p is a suppressor of BC that inhibits proliferation and metastasis, and promotes apoptosis in BC cells as well as suppresses tumor growth in a T24 xenograft mouse model, which could be used as a potential therapeutic approach for BC in future.