Mutual Regulation of MiR-199a-5p and HIF-1α Modulates the Warburg Effect in Hepatocellular Carcinoma

Journal of Cancer
Binkui LiYunfei Yuan

Abstract

The Warburg effect is one of the major metabolic changes of cancer cells, which characterized by high level of glycolysis even in the presence of oxygen. However, the role of microRNAs (miRNAs) in regulating the glycolytic switch in cancer cells has not been well explored. In this study, we demonstrated that miR-199a-5p acts as a suppressor of the Warburg effect in hepatocellular carcinoma (HCC). MiR-199a-5p directly targets the 3'-untranslated region (UTR) of hypoxia-inducible factor-1α (HIF-1α), thereby suppressing glucose uptake, lactate production, cell growth, and expression of HIF-1α downstream glycolytic genes of HCC cells. Moreover, under hypoxic conditions, the expression of miR-199a-5p is suppressed by the up-regulation of HIF-1α. Thus, mutual regulation between miR-199a-5p and HIF-1α forms a positive feedback loop to promote glycolysis in HCC cells. Furthermore, miR-199a-5p is down-regulated in human HCC tissues and its low-level expression is associated with a worse survival of patients with HCC. Our findings suggest that miR-199a-5p/HIF-1α axis is critical in the regulation of the Warburg effect and also implicate miR-199a-5p as a potential therapeutic target for HCC.

Citations

Jan 18, 2018·International Journal of Molecular Sciences·Florian SchuellerChristoph Roderburg
Mar 21, 2018·Molecular and Cellular Biology·Juan F ArandaCarlos Fernández-Hernando
Sep 17, 2020·International Journal of Molecular Sciences·Dobrochna DolickaMichelangelo Foti
Jun 30, 2018·Oxidative Medicine and Cellular Longevity·Oren Tirosh
Oct 15, 2018·Cellular and Molecular Life Sciences : CMLS·Wanli YangDaiming Fan
Jul 8, 2020·Journal of Experimental & Clinical Cancer Research : CR·Jiao FengChuanyong Guo
Jan 29, 2021·International Journal of Molecular Sciences·Dexter L PuckettAhmed Bettaieb
Mar 7, 2021·International Journal of Molecular Sciences·Maria Magdalena BarrecaAlice Conigliaro
May 21, 2021·Journal of Hepatocellular Carcinoma·Laura GramantieriFrancesca Fornari
Apr 5, 2019·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Zhixiong MeiNi Deng

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Methods Mentioned

BETA
surgical resection
transfections
transfection
PCR
flow cytometry
Assay
Protein Assay

Software Mentioned

SPSS ( Statistical Package for the Social Sciences )
GraphPad Prism

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