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

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.