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miRNA Expression Analyses in Prostate Cancer Clinical Tissues
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Androgen-regulated microRNA-135a decreases prostate cancer cell migration and invasion through downregulating ROCK1

A Kroiss1, S Vincent1, M Decaussin-Petrucci2

  • 1Université de Lyon, Ecole Normale Supérieure de Lyon, Université Claude Bernard Lyon 1, Institut de Génomique Fonctionnelle de Lyon (IGFL), Lyon, France.

Oncogene
|July 29, 2014
PubMed
Summary
This summary is machine-generated.

MicroRNA-135a (miR-135a) is activated by androgen signaling in prostate cancer (PCa). Lower miR-135a levels correlate with aggressive PCa and reduced invasion, suggesting it may be a prognostic marker.

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Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Androgen signaling, mediated by the androgen receptor (AR), is critical for prostate cancer (PCa) development and progression.
  • Identifying novel downstream effectors of the AR pathway is essential for understanding PCa mechanisms and developing new therapeutic strategies.

Purpose of the Study:

  • To identify novel microRNA (miRNA) effectors in androgen signaling relevant to prostate cancer.
  • To investigate the role of miR-135a in PCa cell invasion and its potential as a prognostic marker.

Main Methods:

  • High-throughput reverse transcriptase-quantitative PCR to profile miRNA expression in response to androgen stimulation.
  • Androgen stimulation of LNCaP cells and AR binding analysis to confirm direct transcriptional activation of miR-135a.
  • In vitro and in vivo assays (xenografts, wound-healing) to assess the effect of miR-135a on prostate cancer cell invasion.
  • Analysis of ROCK1 and ROCK2 gene expression as direct targets of miR-135a.
  • Immunohistochemistry and analysis of human prostatectomy samples to correlate miR-135a and ROCK1 expression with clinicopathological features.

Main Results:

  • Androgen stimulation upregulated miR-135a expression in LNCaP cells.
  • The androgen receptor (AR) directly activates the transcription of the miR-135a gene.
  • Overexpression of miR-135a reduced in vivo and in vitro invasion of PC-3 prostate cancer cells.
  • miR-135a directly targets and downregulates ROCK1 and ROCK2 expression.
  • Lower miR-135a expression and higher ROCK1 protein levels were observed in high-grade (Gleason score ⩾8) and invasive prostate tumors compared to normal tissues.

Conclusions:

  • miR-135a is a novel downstream effector of the androgen/AR signaling pathway in prostate cancer.
  • The miR-135a/ROCK1 axis plays a role in regulating prostate cancer cell invasion.
  • Reduced miR-135a expression is associated with increased disease aggressiveness and may serve as a prognostic biomarker for human PCa.