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

Hwang,Thomas I‑Sheng; Cuiu,Yu-Chi; Chen,Yen-Chen; Chen,Po-Chun; Tsai,Te-Fu; Chou,Kuang-Yu; Ho,Chao-Yen; Chen,Hung-En; Chang,Peng-Hui; Chang,An-Chen

doi:10.3892/ijo.2023.5514

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

Authors:
- Thomas I‑Sheng Hwang
- Yu-Chi Cuiu
- Yen-Chen Chen
- Po-Chun Chen
- Te-Fu Tsai
- Kuang-Yu Chou
- Chao-Yen Ho
- Hung-En Chen
- Peng-Hui Chang
- An-Chen Chang
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Affiliations: Division of Urology, Department of Surgery, Shin Kong Wu Ho‑Su Memorial Hospital, Taipei 111045, Taiwan, R.O.C., Translational Medicine Center, Research Department, Shin Kong Wu Ho‑Su Memorial Hospital, Taipei 111045, Taiwan, R.O.C.
Published online on: April 20, 2023 https://doi.org/10.3892/ijo.2023.5514
Article Number: 66
Copyright: © Hwang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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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