Tumor suppressive functions of hsa-miR-34a on cell cycle, migration and protective autophagy in bladder cancer

Bladder cancer (BC) cells exhibit a high basal level of autophagy activity, which contributes to the development of a protective mechanism for cellular survival against current treatments. Hsa-microRNA-34a (miR-34a) presents anti-tumor function in several types of cancer. However, the functional mechanism of miR-34a in regulating tumor aggressiveness and protective autophagy of BC remains largely unknown. First, transfected BC cells with miR-34a mimic exhibited LC3-II and p62 accumulation through immunofluorescence staining. It was demonstrated that syntaxin 17 (STX17), which is required for autophagosome-lysosome fusion, was downregulated upon miR-34a mimic treatment. Mechanistically, miR-34a reduced the expression of STX17 proteins that directly bind on STX17 3′-untranslated regions and thus suppressed STX17 mRNA translation to eventually inhibit protective autophagy in BC. Cell viability and colony formation assays revealed that overexpression of miR-34a in BC cells enhances the chemosensitivity of cisplatin, doxorubicin, epirubicin and mitomycin C. Furthermore, miR-34a inhibited cell proliferation and triggered G0/G1 cell cycle arrest by inhibiting cyclin D1 and cyclin E2 protein expression. Moreover, miR-34a suppressed cell motility through the downregulation of epithelial-mesenchymal transition. In summary, miR-34a inhibits cell proliferation, motility and autophagy activity in BC, which can benefit BC treatment.