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Published studies have identified genetic variants, somatic mutations, and changes in gene expression profiles that are associated with hepatocellular carcinoma (HCC), particularly involving genes that encode drug metabolizing enzymes (DMEs). CYP2C9, one of the most abundant and important DMEs, is involved in the metabolism of many carcinogens and drugs and is down-regulated in HCC. To investigate the molecular mechanisms that control CYP2C9 expression, we applied integrative approaches including  in silico ,  in vitro , and  in vivo  analyses to elucidate the role of microRNA hsa-miR-128-3p in the regulation of CYP2C9 expression and translation. RNA electrophoresis mobility shift assays demonstrated a direct interaction between hsa-miR-128-3p and its cognate target, the  CYP2C9  transcript. Furthermore, the expression of a luciferase reporter gene containing the 3′-UTR of  CYP2C9  and the endogenous expression of  CYP2C9  were suppressed by transfection of hsa-miR-128-3p. Importantly, chemically-induced up- or down-regulation of hsa-miR-128-3p correlated inversely with the expression of  CYP2C9 . Finally, an association analysis revealed that the expression of hsa-miR-128-3p is inversely correlated with the expression of  CYP2C9  in HCC tumor tissues. Altogether, the study helped to elucidate the mechanism of  CYP2C9  regulation by hsa-miR-128-3p, and the inverse association in HCC.

Suppression of CYP2C9 by MicroRNA hsa-miR-128-3p in Human Liver Cells and Association with Hepatocellular Carcinoma