LncRNA HOTAIR knockdown inhibits glycolysis by regulating miR-130a-3p/HIF1A in hepatocellular carcinoma under hypoxia.

Abstract

High rate of glycolysis supports hepatocellular carcinoma (HCC) cell growth even in a hypoxic environment. However, the mechanism underlying glycolysis under hypoxia remains largely unknown. Long noncoding RNAs (lncRNAs) play essential roles in regulating glucose metabolism in cancers. This study aimed to explore the role of lncRNA homeobox transcript antisense RNA (HOTAIR) in HCC glycolysis under hypoxia. Thirty-eight HCC patients were recruited. HepG2 and Huh7 cells were used for study in vitro. The expression levels of HOTAIR, microRNA-130a-3p (miR-130a-3p) and hypoxia inducible factor 1 alpha (HIF1A) were measured by quantitative real-time polymerase chain reaction and western blot, respectively. The glycolysis under hypoxia (1 % O2) condition was investigated by glucose consumption, lactate production and hexokinase 2 (HK2) level. The target interaction between miR-130a-3p and HOTIR or HIF1A was analyzed by bioinformatics analysis, luciferase assay, RNA pull-down and RNA immunoprecipitation. We found that HOTAIR expression was enhanced in HCC tissues and cells. Under hypoxia condition, HOTAIR expression was increased and its knockdown inhibited glycolysis in HCC cells. HOTAIR was validated as a decoy of miR-130a-3p and miR-130a-3p deficiency reversed the suppressive effect of HOTAIR silence on glycolysis under hypoxia. HIF1A was indicated as a target of miR-130a-3p and miR-130a-3p overexpression repressed glycolysis under hypoxia by targeting HIF1A. Moreover, HIF1A expression was regulated by HOTAIR and miR-130a-3p. In conclusion, knockdown of HOTAIR suppressed glycolysis by regulating miR-130a-3p and HIF1A in HCC cells treated by hypoxia, elucidating a novel mechanism in HCC glycolysis.

• Authors: Mingxing Hu, Qiang Fu, Chan Jing, Xu Zhang, Tao Qin, Yanfeng Pan
• Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (Biomed Pharmacother) Vol. 125 Pg. 109703 (May 2020) ISSN: 1950-6007 [Electronic] France
• PMID: 32062551 (Publication Type: Journal Article)
• Copyright: Copyright © 2019 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.

Chemical References

• HIF1A protein, human
• HOTAIR long untranslated RNA, human
• Hypoxia-Inducible Factor 1, alpha Subunit
• MIRN130 microRNA, human
• MicroRNAs
• RNA, Long Noncoding
• HK2 protein, human
• Hexokinase

Topics

• Carcinoma, Hepatocellular (genetics, metabolism, pathology)
• Cell Line, Tumor
• Female
• Glycolysis (genetics)
• Hexokinase (metabolism)
• Humans
• Hypoxia
• Hypoxia-Inducible Factor 1, alpha Subunit (metabolism)
• Liver Neoplasms (genetics, metabolism)
• Male
• MicroRNAs (genetics, metabolism)
• RNA, Long Noncoding (genetics, metabolism)