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Published on: April 6, 2012

Genistein downregulates onco-miR-1260b and inhibits Wnt-signalling in renal cancer cells

H Hirata1, K Ueno, K Nakajima

  • 1Department of Urology, San Francisco Veterans Affairs Medical Center and University of California at San Francisco, San Francisco, CA 94121, USA.

British Journal of Cancer
|April 18, 2013
PubMed
Abstract

Insights

Genistein inhibits renal cell carcinoma (RCC) by downregulating miR-1260b, a microRNA that promotes cancer growth. This finding reveals a new mechanism for genistein

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Wnt-signalling is crucial in renal cancer development.
  • Genistein modulates Wnt-signalling in various cancers.
  • MicroRNAs (miRNAs) are key gene regulators.

Purpose of the Study:

  • To investigate genistein's regulatory mechanism on Wnt-signalling in renal cell carcinoma (RCC) via miRNAs.
  • To identify specific miRNAs affected by genistein in RCC.

Main Methods:

  • Assessed genistein's effect on Wnt-signalling using TOPflash reporter assays in RCC cells.
  • Utilized microarray to identify miRNAs downregulated by genistein.
  • Conducted functional analyses and 3'UTR luciferase assays to confirm miRNA targets.

Main Results:

  • Genistein inhibited RCC cell proliferation, invasion, and Wnt-signalling.
  • miR-1260b was significantly upregulated in RCC and downregulated by genistein.
  • High miR-1260b expression correlated with shorter patient survival and promoted RCC progression.

Conclusions:

  • Genistein inhibits Wnt-signalling in renal cancer by downregulating miR-1260b.
  • miR-1260b acts as an oncogenic miRNA in renal cell carcinoma.
  • Target genes sFRP1, Dkk2, and Smad4 are directly regulated by miR-1260b.

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