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Post-transcriptional regulation of OATP2B1 transporter by a microRNA, miR-24.

Abstract：

:Human OATP2B1, a member of organic anion transporting polypeptide family, is expressed in several tissues, including small intestine and liver, and contributes to cellular uptake of endogenous compounds and various drugs. Altered expression of OATP2B1 affects pharmacokinetics of substrate drugs; however, limited information is available on the regulation of OATP2B1 expression. This study aimed to explore microRNAs (miRNAs) that regulate OATP2B1 expression using HEK293 cells transfected with an expression plasmid of OATP2B1 including 3'-UTR (HEK/OATP2B1) and Caco-2 as a model of human intestine. Computational analysis predicted that three miRNAs, miR-143, miR-125b and miR-24, may bind to the 3'-UTR of OATP2B1 mRNA. A luciferase assay using a plasmid containing the 3'-UTR of OATP2B1 gene demonstrated that only miR-24 significantly reduced its expression. The overexpression of miR-24 decreased the expression of OATP2B1 mRNA and protein in HEK/OATP2B1 and Caco-2 cells and uptake of [3H]estrone-3-sulfate by HEK/OATP2B1 cells. However, a statistically significant increase of endogenous OATP2B1 expression was not observed by miR-24 inhibitor in Caco-2 cells. In conclusion, it was found that miR-24 negatively regulates OATP2B1 expression, resulting in suppression of OATP2B1 activity, while its contribution to regulation of apparent expression of OATP2B1 is considered to depend on tissues and cell types.

journal_name

Drug Metab Pharmacokinet

journal_title

Drug metabolism and pharmacokinetics

authors

Liu W,Nakano M,Nakanishi T,Nakajima M,Tamai I

doi

10.1016/j.dmpk.2020.07.007

subject

Has Abstract

pub_date

2020-12-01 00:00:00

pages

515-521

issue

6

eissn

1347-4367

issn

1880-0920

pii

S1347-4367(20)30404-3

journal_volume

35

pub_type

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