miR-4458 suppresses glycolysis and lactate production by directly targeting hexokinase2 in colon cancer cells

• Published in: Biochemical and biophysical research communications Vol. 469; no. 1; pp. 37 - 43
• Main Authors: Qin, Yaguang, Cheng, Chuanyao, Lu, Hong, Wang, Yaqiu
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.01.2016
• Subjects: 60 APPLIED LIFE SCIENCES; anaerobic conditions; bioinformatics; Cell Line, Tumor; CELL PROLIFERATION; Colon cancer; Colonic Neoplasms - metabolism; colorectal neoplasms; Genes, Tumor Suppressor; Glucose - metabolism; GLYCOLYSIS; hepatoma; HEPATOMAS; Hexokinase - metabolism; Hexokinase2 (HK2); Humans; INHIBITION; Lactate; LACTATES; Lactic Acid - metabolism; LARGE INTESTINE; LUCIFERASE; MESSENGER-RNA; MicroRNAs - metabolism; miR-4458; neoplasm cells; Proliferation; RNA interference; Hexokinase2 (HK2); Glycolysis; Colon cancer; Proliferation; miR-4458; Lactate
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2015.11.066

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. •miR-4458 is down-regulated in colon cancer cells.•miR-4458 suppresses proliferation, glycolysis, and lactate production.•HK2 is a target of miR-4458.•HK2 knockdown inhibits proliferation, glycolysis, and lactate production.