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.

中文翻译：

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外泌体 miR-375-3p 的作用：通过 Wnt/β-catenin 途径抑制膀胱癌的潜在抑制因子

miR-375-3p 是膀胱癌 (BC) 中显着下调的 miRNA。然而，其在 BC 监管中的作用仍不清楚。在这项研究中，我们报道了 miR-375-3p 过表达抑制了 BC 细胞的增殖和迁移并促进了细胞凋亡。Frizzled-8 (FZD8) 基因被鉴定为直接的 miR-375-3p 靶向基因。miR-375-3p 通过直接抑制 FZD8 的表达来阻断 Wnt/β-catenin 通路和下游分子 Cyclin D1 和 c-Myc，它可以增加 caspase 1 和 caspase 3 的表达并促进 T24 细胞凋亡。miR-375-3p在荷膀胱肿瘤裸鼠体内也显示出显着的抑制作用，这可以通过肿瘤组织中肿瘤体积和Ki67增殖指数的减少来证明。总的来说，miR-375-3p 是 BC 的抑制因子，可抑制增殖和转移，