The miR-17-92 cluster is over expressed in and has an oncogenic effect on renal cell carcinoma

Tsz-Fung F Chow1, Marina Mankaruos, Andreas Scorilas

  • 1Department of Laboratory Medicine and Keenan Research Centre, Li Ka Shing Knowledge Institute, Toronto, Ontario, Canada.

The Journal of Urology
|December 22, 2009
PubMed
Abstract

Insights

MicroRNAs (miRNAs) are dysregulated in clear cell renal cell carcinoma (ccRCC). miR-20a inhibits ccRCC proliferation, while miR-17-5p promotes it, suggesting therapeutic potential.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • MicroRNAs (miRNAs) are small, noncoding RNAs with critical roles in gene regulation.
  • Aberrant miRNA expression is a hallmark of many cancers, including clear cell renal cell carcinoma (ccRCC).
  • Previous work identified 80 dysregulated miRNAs in ccRCC.

Purpose of the Study:

  • Validate the overexpression of the miR-17-92 cluster in ccRCC.
  • Investigate the functional impact of miR-17-5p and miR-20a on ccRCC cell proliferation.
  • Elucidate the role of miRNA dysregulation in ccRCC pathogenesis using bioinformatics.

Main Methods:

  • Quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) for miRNA expression validation.
  • Renal adenocarcinoma cell line (ACHN) model to assess miRNA effects on proliferation.
  • In silico analyses, including target prediction and pattern matching with genomic aberrations.

Main Results:

  • miR-17-92 cluster overexpression was confirmed in ccRCC via qRT-PCR.
  • miR-20a inhibition significantly reduced ccRCC cell proliferation in a dose-dependent manner.
  • miR-17-5p transfection increased proliferation, an effect reversed by its inhibitor. Bioinformatics identified 10 miRNA clusters and linked miRNA dysregulation to chromosomal aberrations in 37.5% of cases. Key ccRCC molecules (HIFs, mTOR, VEGF, VHL) were predicted as miRNA targets.

Conclusions:

  • Numerous dysregulated proteins in ccRCC are potential miRNA targets.
  • Phylogenetically conserved miRNAs are frequently dysregulated in ccRCC.
  • Specific miRNAs, like miR-20a and miR-17-5p, play opposing roles in ccRCC proliferation, offering potential therapeutic avenues.

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