title: miR-592/WSB1/HIF-1α axis inhibits glycolytic metabolism to decrease hepatocellular carcinoma growth.
abstract: Hepatocellular carcinoma (HCC) cells rapidly switch their energy source from oxidative phosphorylation to glycolytic metabolism in order to efficiently proliferate. However, the molecular mechanisms responsible for this switch remain unclear. In this study, we found that miR-592 was frequently downregulated in human HCC tissues and cell lines, and its downregulation was closely correlated with aggressive clinicopathological features and poor prognosis of HCC patients. Overexpression of miR-592 inhibited aerobic glycolysis and proliferation in HCC cells in vitro. Conversely, knockdown of miR-592 promoted HCC growth in both subcutaneous injection and orthotopic liver tumor implantation models in vivo. Mechanistically, miR-592 downregulation in human HCCs was correlated with an upregulation of WD repeat and SOCS box containing 1 (WSB1). We further showed that miR-592 directly binds to the 3'-UTR of the WSB1 gene, thus disrupting hypoxia inducible factor-1α (HIF-1α) protein stabilization. In turn, overexpression of WSB1 in HCC cells rescued decreased HIF-1α expression, glucose uptake, and HCC growth induced by miR-592. Collectively, our clinical data and functional studies suggest that miR-592 is a new robust inhibitor of the Warburg effect and a promising therapeutic target for HCC treatment.
authors.affiliation: Department of Pharmacy, General Hospital of Guangzhou Military Command of People's Liberation Army, Guangzhou, Guangdong, P. R. China.|Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, P. R. China.
authors.forename: Yan-Yan
authors.initials: YY
authors.lastname: Jia
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, P. R. China.
authors.forename: Jin-Yi
authors.initials: JY
authors.lastname: Zhao
authors.affiliation: Department of Pharmacy, General Hospital of Guangzhou Military Command of People's Liberation Army, Guangzhou, Guangdong, P. R. China.
authors.forename: Bing-Ling
authors.initials: BL
authors.lastname: Li
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, P. R. China.
authors.forename: Kai
authors.initials: K
authors.lastname: Gao
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, P. R. China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Song
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, P. R. China.
authors.forename: Mei-You
authors.initials: MY
authors.lastname: Liu
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, P. R. China.
authors.forename: Xiao-Juan
authors.initials: XJ
authors.lastname: Yang
authors.affiliation: Department of Oncology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, P. R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Xue
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, P. R. China.
authors.forename: Ai-Dong
authors.initials: AD
authors.lastname: Wen
authors.affiliation: Department of Pharmacy, General Hospital of Guangzhou Military Command of People's Liberation Army, Guangzhou, Guangdong, P. R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Shi
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D006019:Glycolysis / Q000502:physiology; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D016513:Mice, SCID; D035683:MicroRNAs / Q000378:metabolism*; D011379:Prognosis; D011506:Proteins / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D047908:Intracellular Signaling Peptides and Proteins; C000588991:MIRN592 microRNA, human; D035683:MicroRNAs; D011506:Proteins; C120287:WSB1 protein, human
keywords: WSB1; glycolysis; hepatocellular carcinoma; hypoxia inducible factor-1α; miR-592