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miR-592/WSB1/HIF-1α axis inhibits glycolytic metabolism to decrease hepatocellular carcinoma growth.

Yan-Yan Jia1,2, Jin-Yi Zhao2, Bing-Ling Li1

  • 1Department of Pharmacy, General Hospital of Guangzhou Military Command of People's Liberation Army, Guangzhou, Guangdong, P. R. China.

Oncotarget
|May 7, 2016
PubMed
Summary

MicroRNA-592 (miR-592) inhibits hepatocellular carcinoma (HCC) growth by suppressing the Warburg effect. Its downregulation in HCC patients correlates with poor prognosis, suggesting miR-592 as a potential therapeutic target.

Keywords:
WSB1glycolysishepatocellular carcinomahypoxia inducible factor-1αmiR-592

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Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Hepatocellular carcinoma (HCC) cells exhibit altered metabolism, favoring glycolysis (Warburg effect) for proliferation.
  • The precise molecular regulators driving this metabolic shift in HCC remain incompletely understood.

Purpose of the Study:

  • To investigate the role of microRNA-592 (miR-592) in regulating HCC metabolism and tumor progression.
  • To elucidate the molecular mechanism by which miR-592 influences HCC growth.

Main Methods:

  • Analysis of miR-592 expression in HCC tissues and cell lines.
  • In vitro studies involving miR-592 overexpression and knockdown in HCC cells.
  • In vivo tumor growth models (subcutaneous and orthotopic).
  • Luciferase reporter assays to confirm direct binding of miR-592 to WSB1 mRNA.
  • Western blot analysis to assess protein levels (WSB1, HIF-1α).

Main Results:

  • miR-592 was significantly downregulated in HCC tissues and correlated with aggressive features and poor patient prognosis.
  • Overexpression of miR-592 suppressed aerobic glycolysis and HCC cell proliferation in vitro.
  • miR-592 knockdown promoted HCC growth in vivo.
  • miR-592 directly targets WD repeat and SOCS box containing 1 (WSB1), inhibiting its expression.
  • miR-592 disrupts hypoxia inducible factor-1α (HIF-1α) stabilization via WSB1 regulation.
  • WSB1 overexpression reversed the effects of miR-592 on HIF-1α, glucose uptake, and HCC growth.

Conclusions:

  • miR-592 acts as a tumor suppressor in HCC by inhibiting the Warburg effect.
  • The miR-592/WSB1/HIF-1α axis is a critical pathway in HCC metabolic reprogramming and progression.
  • miR-592 represents a promising therapeutic target for hepatocellular carcinoma treatment.