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MicroRNA-10a promotes granulosa cells tumor development via PTEN-AKT/Wnt regulatory axis

Jiajie Tu1,2,3, Hoi-Hung Cheung1,2, Gang Lu1,2,4

  • 1School of Biomedical Sciences, The Chinese University of Hong Kong, Faculty of Medicine, the Chinese University of Hong Kong, Hong Kong SAR, China.

Cell Death & Disease
|October 24, 2018
PubMed

Insights

MicroRNA-10a (miR-10a) promotes ovarian cancer growth by targeting PTEN and activating Akt/Wnt pathways. Inhibiting miR-10a suppressed tumor progression in preclinical models, highlighting its potential as a therapeutic target.

Area of Science:

  • Molecular Biology
  • Oncology
  • Gene Regulation

Background:

  • MicroRNA-10 family members can disrupt granulosa cell (GC) development.
  • Granulosa cell tumors (GCTs) are a significant subtype of ovarian cancer.

Purpose of the Study:

  • To investigate the role of miR-10a in the development and progression of granulosa cell tumors (GCTs).
  • To identify the molecular mechanisms underlying miR-10a's function in GCTs.

Main Methods:

  • Analysis of miR-10a expression in GCT tissues.
  • In vitro studies involving forced miR-10a expression and miR-10a knockout in GC cells.
  • In vivo validation using orthotopic and heterotopic GCT mouse models.
  • RNA-sequencing, FISH, Western blot, and luciferase reporter assays to identify targets and pathways.

Main Results:

  • Elevated miR-10a levels were observed in malignant GCT tissues.
  • Forced miR-10a expression enhanced GCT cell proliferation, migration, invasion, hormone production, and chemoresistance.
  • miR-10a knockout using CRISPR-Cas9 repressed aggressive GCT phenotypes.
  • PTEN was identified as a direct target of miR-10a, with Akt and Wnt pathways being associated oncogenic pathways.

Conclusions:

  • miR-10a acts as an oncomiR in GCT development.
  • miR-10a promotes GCT progression by targeting PTEN and activating Akt and Wnt signaling pathways.
  • Targeting miR-10a represents a potential therapeutic strategy for ovarian cancer.

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