MicroRNA-181a promotes docetaxel resistance in prostate cancer cells

Cameron M Armstrong1, Chengfei Liu1, Wei Lou1

  • 1Department of Urology, University of California Davis, Sacramento, California.

The Prostate
|May 10, 2017
PubMed
Abstract

Insights

MicroRNAs, specifically miR-181a, drive resistance to docetaxel and cabazitaxel in castration resistant prostate cancer (CRPC). Inhibiting miR-181a restores treatment sensitivity by affecting p53 phosphorylation and apoptosis.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Docetaxel is a primary treatment for castration-resistant prostate cancer (CRPC).
  • Acquired resistance to docetaxel limits its long-term efficacy in CRPC patients.
  • Mechanisms of docetaxel resistance, including the role of microRNAs, are not fully understood.

Purpose of the Study:

  • To investigate the role of miR-181a in the development of docetaxel resistance in CRPC.
  • To determine if modulating miR-181a levels can overcome docetaxel resistance.

Main Methods:

  • Quantitative real-time PCR to measure miR-181a expression in docetaxel-resistant prostate cancer cells.
  • Transfection with miR-181a mimics or antisense oligonucleotides to modulate expression.
  • Cell viability assays, Western blotting for ABCB1 and phospho-p53, and apoptosis assays (ELISA).

Main Results:

  • miR-181a was significantly overexpressed in docetaxel-resistant cells.
  • Overexpressing miR-181a induced resistance to docetaxel and cabazitaxel.
  • Knockdown of miR-181a restored sensitivity to both drugs and induced apoptosis via p53 phosphorylation.
  • miR-181a did not affect ABCB1 expression or activity.

Conclusions:

  • miR-181a overexpression is a key factor in CRPC resistance to docetaxel and cabazitaxel.
  • Inhibiting miR-181a can re-sensitize CRPC cells to chemotherapy.
  • The mechanism involves the modulation of p53 phosphorylation and apoptosis.

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