Cancer cells are addictively dependent on glycolysis even in an oxygen-rich condition. However, the mechanism underlying micro (mi)RNA regulation of aerobic glycolysis in cancer cells has not been fully understood. Here, we demonstrated that the expression of miR-142-3p was lower in hepatocellular carcinoma (HCC) as compared to adjacent non-tumor samples, which was confirmed in The Cancer Genome Atlas (TCGA) HCC cohorts and Gene Expression Omnibus (GEO) datasets. Function and pathway analysis showed that miR-142-3p was most relevent with metabolism. As predicted, the overexpression of miR-142-3p inhibited aerobic glycolysis and thus proliferation of HCC cells. Mechanistically, we identified lactate dehydrogenase A (LDHA), one of the important catalyticase for aerobic glycolysis, as the target of miR-142-3p. Exogenous expression of miR-142-3p reduced the protein levels of LDHA in both SK-Hep-1 and Huh7 cells. Dual luciferase report assays showed the expression of LDHA was directly modulated by miR-142-3p. miR-142-3p-induced deduction of aerobic glycolysis and proliferation were reversed by LDHA overexpression. Taken together, these results indicate that miR-142-3p could act as a tumor suppressor in HCC by targeting LDHA, suggesting new therapeutic targets for HCC treatment.
Keywords: Aerobic glycolysis; Hepatocellular carcinoma; LDHA; Proliferation; miR-142-3p.
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