The inhibitory effects of AR/miR-190a/YB-1 negative feedback loop on prostate cancer and underlying mechanism

Sci Rep. 2015 Aug 28:5:13528. doi: 10.1038/srep13528.

Abstract

Prostate cancer at advanced stages including metastatic and castration-resistant cancer remains incurable due to the lack of effective therapies. MiR-190a belongs to the small noncoding RNA family and has an important role in breast cancer metastasis. However, it is still unknown whether miR-190a plays a role in prostate cancer development. Herein, we first observed AR/miR-190a/YB-1 forms an auto-regulatory negative feedback loop in prostate cancer: miR-190a expression was down-regulated by AR activation; YB-1 functions are as an AR activator; miR-190a inhibited AR expression and transactivation through direct binding to 3'UTR of YB-1 gene. MiR-190a contributes the human prostate cancer cell growth through AR-dependent signaling. Moreover, we examined the expression of miR-190a and observed a significant decrease in human prostate cancers. Reduced expression of miR-190a was inversely correlated to AR levels of prostate cancer patients, and patients with higher miR-190a expression in their tumor have improved tumor-free survival. Taken together, our findings identified a biochemical and functional link between miR-190a with reduced expression in advanced prostate cancer, YB-1 and AR signaling in prostate cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / genetics
  • Androgens / pharmacology
  • Base Sequence
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Feedback, Physiological* / drug effects
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Male
  • MicroRNAs / metabolism*
  • Molecular Sequence Data
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / pathology
  • Protein Binding / drug effects
  • Receptors, Androgen / genetics
  • Receptors, Androgen / metabolism*
  • Signal Transduction / drug effects
  • Signal Transduction / genetics
  • Transcriptional Activation / drug effects
  • Transcriptional Activation / genetics
  • Y-Box-Binding Protein 1 / metabolism*

Substances

  • 3' Untranslated Regions
  • AR protein, human
  • Androgens
  • MIRN190 microRNA, human
  • MicroRNAs
  • Receptors, Androgen
  • Y-Box-Binding Protein 1
  • YBX1 protein, human