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

Thomas I-Sheng Hwang1, Yu-Chi Cuiu2, Yen-Chen Chen2

  • 1Division of Urology, Department of Surgery, Shin Kong Wu Ho‑Su Memorial Hospital, Taipei 111045, Taiwan, R.O.C.

International Journal of Oncology
|April 21, 2023
PubMed

Insights

MicroRNA-34a inhibits bladder cancer (BC) cell proliferation, motility, and protective autophagy by downregulating syntaxin 17. This enhances sensitivity to chemotherapy, offering a potential therapeutic strategy for BC treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Bladder cancer (BC) cells display high autophagy, aiding survival against treatments.
  • Hsa-microRNA-34a (miR-34a) exhibits anti-tumor properties in various cancers.
  • The role of miR-34a in BC aggressiveness and autophagy regulation is unclear.

Purpose of the Study:

  • To investigate the mechanism by which miR-34a regulates tumor aggressiveness and protective autophagy in bladder cancer.
  • To determine the effect of miR-34a on BC cell chemosensitivity, proliferation, cell cycle, and motility.

Main Methods:

  • Transfection of BC cells with miR-34a mimic.
  • Immunofluorescence staining for LC3-II and p62.
  • Western blotting to assess STX17, cyclin D1, and cyclin E2 protein levels.
  • Cell viability, colony formation, and cell motility assays.

Main Results:

  • miR-34a mimic transfection led to LC3-II and p62 accumulation, indicating autophagy modulation.
  • Syntaxin 17 (STX17) expression was downregulated by miR-34a through direct binding to its 3'-UTR, inhibiting autophagosome-lysosome fusion.
  • Overexpression of miR-34a enhanced BC cell sensitivity to cisplatin, doxorubicin, epirubicin, and mitomycin C.
  • miR-34a inhibited cell proliferation, induced G0/G1 cell cycle arrest, and suppressed cell motility via epithelial-mesenchymal transition downregulation.

Conclusions:

  • miR-34a suppresses protective autophagy in BC by inhibiting STX17-mediated autophagosome-lysosome fusion.
  • miR-34a enhances chemosensitivity and inhibits proliferation, cell cycle progression, and motility in bladder cancer.
  • miR-34a demonstrates potential as a therapeutic agent for bladder cancer treatment.
Keywords:
autophagybladder cancerhsa‑microRNA‑34amotilitysyntaxin 17

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