title: miR-4458 suppresses glycolysis and lactate production by directly targeting hexokinase2 in colon cancer cells.
abstract: miR-4458, a new tumor-suppressor, was reported to down-regulated in human hepatocellular carcinoma. The expression status, roles and inhibitory mechanisms of miR-4458 in other tumors still need to be clarified. The aim of this study is to investigate the effects of miR-4458 and to elucidate the potential mechanism in colon cancer cells. Using bioinformatic databases, we predicted that hexokinase2 (HK2), a rate-limiting enzyme in the glycolytic pathway, was a target of miR-4458, so the effects of miR-4458 on glycolysis and lactate production was assessed in colon cancer cells. We found that miR-4458 was down-regulated and HK2 was up-regulated in colon cancer cells. Overexpression of miR-4458 inhibited proliferation, glycolysis, and lactate production under both normoxic and hypoxic conditions. Luciferase activity assays showed that HK2 was a direct target of miR-4458. Moreover, knockdown of HK2 by specific RNAi also suppressed proliferation, glycolysis, and lactate production under both normoxic and hypoxic conditions. In conclusion, our findings suggested that miR-4458 inhibited the progression of colon cancer cells by inhibition of glycolysis and lactate production via directly targeting HK2 mRNA.
authors.affiliation: Department of Oncology, Huaihe Hospital of Henan University, Kaifeng, Henan, 475000, PR China.
authors.forename: Yaguang
authors.initials: Y
authors.lastname: Qin
authors.affiliation: Department of Oncology, Huaihe Hospital of Henan University, Kaifeng, Henan, 475000, PR China.
authors.forename: Chuanyao
authors.initials: C
authors.lastname: Cheng
authors.affiliation: Department of Oncology, Huaihe Hospital of Henan University, Kaifeng, Henan, 475000, PR China. Electronic address: honglu6512@163.com.
authors.forename: Hong
authors.initials: H
authors.lastname: Lu
authors.affiliation: Department of Oncology, Huaihe Hospital of Henan University, Kaifeng, Henan, 475000, PR China.
authors.forename: Yaqiu
authors.initials: Y
authors.lastname: Wang
mesh_terms: D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000378:metabolism*; D016147:Genes, Tumor Suppressor; D005947:Glucose / Q000378:metabolism*; D006019:Glycolysis; D006593:Hexokinase / Q000378:metabolism*; D006801:Humans; D019344:Lactic Acid / Q000378:metabolism*; D035683:MicroRNAs / Q000378:metabolism*
chemical_list: C000597135:MIRN-648 microRNA, human; D035683:MicroRNAs; D019344:Lactic Acid; D006593:Hexokinase; D005947:Glucose
keywords: Colon cancer; Glycolysis; Hexokinase2 (HK2); Lactate; Proliferation; miR-4458