Loss of mir-146a function in hormone-refractory prostate cancer

Shi-Lung Lin1, Angela Chiang, Donald Chang

  • 1Department of Cell and Neurobiology, Keck School of Medicine, BMT-403, University of Southern California, 1333 San Pablo Street, Los Angeles, CA 90033, USA. lins@usc.edu

RNA (New York, N.Y.)
|January 5, 2008
PubMed

Insights

MicroRNA (miRNA) expression patterns correlate with prostate cancer progression. Restoring mir-146a, a down-regulated miRNA, suppressed tumor growth and metastasis by targeting ROCK1, suggesting its tumor-suppressor role.

Area of Science:

  • Molecular Biology
  • Oncology
  • Genetics

Background:

  • MicroRNA (miRNA) expression is linked to human prostate cancer cell differentiation.
  • MiRNAs regulate tumorigenicity by silencing oncogenes or tumor suppressor genes.

Purpose of the Study:

  • To identify differentially expressed miRNAs in androgen-independent prostate cancer cells compared to androgen-dependent cells.
  • To investigate the functional role of mir-146a in suppressing prostate cancer progression.

Main Methods:

  • miRNA microarray analysis to detect miRNA expression patterns.
  • Fluorescent in situ hybridization (FISH) assays on human prostate cancer tissue arrays.
  • In vitro tumorigenicity assays involving constitutive expression of mir-146a.

Main Results:

  • Eight miRNAs were down-regulated and three were up-regulated in androgen-independent prostate cancer cells.
  • Mir-146a expression suppressed >82% of ROCK1 expression in PC3 cells.
  • Mir-146a reduced cell proliferation, invasion, and metastasis.

Conclusions:

  • Mir-146a acts as a tumor suppressor in prostate cancer.
  • Mir-146a may modulate hyaluronan/ROCK1-mediated tumorigenicity in androgen-dependent prostate cancer.

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