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

Abstract

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.

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Survival study of small cell neuroendocrine carcinoma of the bladder: an analysis using data from the SEER Program

“…A study conducted by Cheng et al (Cheng et al 2004) indicated that the main susceptible population of SCNEC were older adults with smoking history, bladder stones, urinary tract infections, and other susceptibility factors. In addition, SCNEC was also reported to be related to the loss of tumor suppressor genes (e.g., p16), the ampli cation of oncogenic genes (e.g., c-Myc) and the methylation of tumor suppressor factors (Hwang et al 2023; Ke et al 2022).…”