Tumor‑suppressive microRNA‑223 targets WDR62 directly in bladder cancer

Satoshi Sugita1, Hirofumi Yoshino1, Masaya Yonemori1

  • 1Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890‑8520, Japan.

Insights

MicroRNA-223 (miR-223) acts as a tumor suppressor in bladder cancer (BC). Restoring miR-223 inhibits BC cell aggressiveness and promotes apoptosis by targeting oncogenic WDR62.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • The role of microRNA-223 (miR-223) in cancer is context-dependent, acting as both a tumor suppressor and oncogene.
  • Previous deep sequencing identified downregulated miR-223 in clinical bladder cancer (BC) specimens, suggesting a tumor-suppressive role.

Purpose of the Study:

  • To investigate the functional roles of miR-223 in bladder cancer.
  • To identify miR-223 targets and elucidate its mechanism in BC oncogenesis.

Main Methods:

  • Analysis of miR-223 expression in clinical BC specimens and TCGA database.
  • Restoration of miR-223 expression and WDR62 knockdown in BC cells.
  • Luciferase assay to confirm direct binding between miR-223 and WDR62.
  • Assessment of tumor aggressiveness and apoptosis (caspase-3/7 activation).

Main Results:

  • miR-223 expression was significantly decreased in BC, correlating with lymphovascular invasion and distant metastasis.
  • Restoring miR-223 inhibited BC aggressiveness and induced apoptosis.
  • WD repeat domain 62 (WDR62) was identified as a direct miR-223 target, with its expression linked to higher tumor grade and stage.
  • WDR62 knockdown suppressed BC aggressiveness and induced apoptosis.

Conclusions:

  • miR-223 functions as a tumor suppressor in bladder cancer.
  • Oncogenic WDR62 is a novel target of miR-223, providing insights into BC oncogenesis.

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