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 develop–ment 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 aggres–siveness and protective autophagy of BC remains largely unknown. First, transfected BC cells with miR–34a mimic exhibited LC3–II and p62 accumulation through immuno–fluorescence 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, doxo–rubicin, 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 expres–sion. 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.