RRC ID 67064
Author Tajiri A, Hirota T, Kawano S, Yonamine A, Ieiri I.
Title Regulation of Organic Anion Transporting Polypeptide 2B1 Expression by MicroRNA in the Human Liver.
Journal Mol Pharm
Abstract Organic anion transporting polypeptide 2B1 (OATP2B1, SLCO2B1) is an uptake transporter expressed in several tissues, including the liver, intestine, brain, kidney, and skeletal muscle. Hepatocyte nuclear factor 4 alpha (HNF4α) is known as an important transcriptional factor of OATP2B1 in the liver. It has been reported that there are large interindividual differences in OATP2B1 mRNA and protein expressions in human livers. The mechanism causing the interindividual differences in OATP2B1 expression is still unclear. MicroRNAs (miRNAs) control gene expression by leading translational repression and/or degradation of the target mRNA. There is no significant correlation between OATP2B1 mRNA and protein expression, suggesting that post-transcriptional regulating mechanisms, such as miRNAs, play an important role in the interindividual differences in OATP2B1 expression. In this study, we hypothesized that certain miRNAs cause the interindividual differences in OATP2B1 expression in the human liver. In silico analysis showed that miR-24 was a candidate miRNA regulating OATP2B1 expression. It has been reported that miR-24 degrades HNF4α mRNA expression. We revealed that the miR-24 expression level was negatively correlated with OATP2B1 mRNA, protein, and HNF4α mRNA expression levels in human livers. Transfection by the miR-24 precursor decreased the luciferase activity in the transfected cells with the vector containing the OATP2B1 3' untranslated region (3'UTR) or SLCO2B1 promoter region. In HepaRG cells, miR-24 decreased the OATP2B1 and HNF4α expression levels. These results suggest that miR-24 represses not only the translation of OATP2B1 but also the transcription of OATP2B1 by HNF4α mRNA degradation.
Volume 17(8)
Pages 2821-2830
Published 2020-8-3
DOI 10.1021/acs.molpharmaceut.0c00193
PMID 32602343
MeSH Biological Transport / physiology Cell Line, Tumor Gene Expression Regulation / physiology Hep G2 Cells Hepatocyte Nuclear Factor 4 / metabolism Humans Liver / metabolism* MicroRNAs / metabolism* Organic Anion Transporters / metabolism* RNA, Messenger / metabolism
IF 4.321
Human and Animal Cells Hep G2(RCB1886)