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Front Genet. 2019 May 28;10:484. doi: 10.3389/fgene.2019.00484. eCollection 2019.

Transcriptional Repression of CYP3A4 by Increased miR-200a-3p and miR-150-5p Promotes Steatosis in vitro.

Huang Z1,2, Wang M1,3, Liu L1, Peng J1,2, Guo C1, Chen X4, Huang L1,2, Tan J5, Yang G1,2.

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Center for Clinical Pharmacology, The Third Xiangya Hospital, Central South University, Changsha, China.
Department of Pharmacy, The Third Xiangya Hospital, Central South University, Changsha, China.
Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, China.
Institute of Clinical Pharmacology, Central South University, Changsha, China.
Center for Medical Genetics, Life Science School, Central South University, Changsha, China.


Hepatic cytochrome P450 enzyme activities correlate with non-alcoholic fatty liver disease (NAFLD) and hepatic steatosis. The decreased activity of CYP3A4, an important drug-metabolizing enzyme, is associated with the progression of NAFLD. CYP3A4 is predicted as a target gene of miR-200a-3p and miR-150-5p by MicroInspector and TargetScan algorithms analyses. Here, we found decreased CYP3A4 and increased miR-200a-3p and miR-150-5p in LO2 cells with free fatty acid (FFA)-induced steatosis. Dual-luciferase assay confirmed that both miR-200a-3p and miR-150-5p targeted the 3'-untranslated region (3'-UTR) of CYP3A4 and that such interaction was abolished by miRNA binding site mutations in 3'-UTR of CYP3A4. Using miR-200a-3p and miR-150-5p mimics and inhibitors, we further confirmed that endogenous CYP3A4 was regulated posttranscriptionally by miR-200a-3p or miR-150-5p. Moreover, miR-200a-3p and miR-150-5p inhibitors attenuated FFA-induced steatosis in LO2 cells, and such effect was dependent on CYP3Y4 expression. These results suggest that miR-200a-3p and miR-150-5p, through directly targeting 3'-UTR of CYP3A4, contribute to the development of FFA-induced steatosis.


CYP3A4; LO2 cell line; miR-150-5p; miR-200a-3p; non-alcoholic fatty liver disease

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