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Published on: May 16, 2012

MicroRNAs are mediators of androgen action in prostate and muscle

Ramesh Narayanan1, Jinmai Jiang, Yuriy Gusev

  • 1Preclinical Research and Development, GTx, Inc, Memphis, Tennessee, United States of America. rnarayanan@gtxinc.com

Plos One
|November 5, 2010
PubMed

Insights

MicroRNAs (miRs) are essential for androgen receptor (AR) function. This study reveals a feedback loop where androgens regulate miRs, which in turn control AR activity, crucial for male development and preventing androgen insensitivity syndrome (AIS).

Area of Science:

  • Endocrinology
  • Molecular Biology
  • Genetics

Background:

  • Androgen receptor (AR) is vital for male development and tissue function.
  • Impaired AR function leads to androgen insensitivity syndrome (AIS).
  • The role of microRNAs (miRs) in AR signaling is not fully understood.

Purpose of the Study:

  • To investigate the interaction between AR and miR signaling pathways.
  • To elucidate the function of miRs in regulating AR activity.
  • To understand the molecular mechanisms underlying AR function and dysfunction.

Main Methods:

  • Studied miR expression changes in Sprague-Dawley rats after castration and dihydrotestosterone (DHT) or selective androgen receptor modulator treatment.
  • Utilized DICER knockout in LNCaP prostate cancer cells and mouse tissues to assess miR processing impact on AR function.
  • Analyzed the expression of AR corepressors NCoR and SMRT following DICER knockdown.

Main Results:

  • Castration reduced miR expression in rat prostate and muscle; DHT or selective androgen receptor modulators reversed this effect.
  • DICER knockout in LNCaP cells and mouse tissues impaired AR function, mimicking AIS.
  • DICER knockdown increased the expression of AR corepressors NCoR and SMRT.

Conclusions:

  • MicroRNAs play a critical role in androgen receptor function.
  • A feedback loop exists between miRs, corepressors (NCoR, SMRT), and AR.
  • This miR-mediated regulation is essential for AR function in non-cancerous androgen-responsive tissues.

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