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Regulation of Organic Anion Transporting Polypeptide 2B1 Expression by MicroRNA in the Human Liver
journal contribution
posted on 2020-06-30, 11:34 authored by Ayaka Tajiri, Takeshi Hirota, Sasagu Kawano, Akira Yonamine, Ichiro IeiriOrganic 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.
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Keywords
OATP 2B expressionpolypeptide 2 B 1interindividual differencesOATP 2BPolypeptide 2 B 1 ExpressionHNF 4α expression levelsHNF 4α mRNA degradationmiR -24 degrades HNF 4α mRNA expressioncontrol gene expressionSLCO 2B promoter regionmiR -24 precursormiR -24 expression levelHuman Liver Organic anionmiR -24miR -24 repressesOATP 2B SLCO 2BOATP 2B mRNAHNF 4α mRNA expression levelsUTR
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