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Regulation of Organic Anion Transporting Polypeptide 2B1 Expression by MicroRNA in the Human Liver.
Molecular Pharmaceutics ( IF 4.5 ) Pub Date : 2020-06-30 , DOI: 10.1021/acs.molpharmaceut.0c00193 Ayaka Tajiri 1 , Takeshi Hirota 1 , Sasagu Kawano 1 , Akira Yonamine 1 , Ichiro Ieiri 1
Molecular Pharmaceutics ( IF 4.5 ) Pub Date : 2020-06-30 , DOI: 10.1021/acs.molpharmaceut.0c00193 Ayaka Tajiri 1 , Takeshi Hirota 1 , Sasagu Kawano 1 , Akira Yonamine 1 , Ichiro Ieiri 1
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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.
中文翻译：
MicroRNA在人肝中调节有机阴离子转运多肽2B1表达的能力。
有机阴离子转运多肽2B1（OATP2B1，SLCO2B1）是一种在多种组织中表达的摄取转运蛋白，包括肝，肠，脑，肾和骨骼肌。肝细胞核因子4α（HNF4α）是肝脏中OATP2B1的重要转录因子。据报道，人肝脏中OATP2B1 mRNA和蛋白质表达的个体差异很大。引起OATP2B1表达个体差异的机制仍不清楚。MicroRNA（miRNA）通过导致目标mRNA的翻译抑制和/或降解来控制基因表达。OATP2B1 mRNA与蛋白表达之间没有显着相关性，表明转录后调控机制（例如miRNA）在OATP2B1表达的个体差异中起重要作用。在这个研究中，计算机分析表明，miR-24是调节OATP2B1表达的候选miRNA。据报道，miR-24降解HNF4αmRNA表达。我们发现，miR-24表达水平与人肝脏中OATP2B1 mRNA，蛋白质和HNF4αmRNA表达水平呈负相关。使用含有OATP2B1 3'非翻译区（3'UTR）或SLCO2B1启动子区的载体，miR-24前体的转染降低了转染细胞中的萤光素酶活性。在HepaRG细胞中，miR-24降低了OATP2B1和HNF4α的表达水平。这些结果表明，miR-24不仅通过HNF4αmRNA降解抑制OATP2B1的翻译，而且抑制OATP2B1的转录。
更新日期：2020-08-03
中文翻译：
MicroRNA在人肝中调节有机阴离子转运多肽2B1表达的能力。
有机阴离子转运多肽2B1（OATP2B1，SLCO2B1）是一种在多种组织中表达的摄取转运蛋白，包括肝，肠，脑，肾和骨骼肌。肝细胞核因子4α（HNF4α）是肝脏中OATP2B1的重要转录因子。据报道，人肝脏中OATP2B1 mRNA和蛋白质表达的个体差异很大。引起OATP2B1表达个体差异的机制仍不清楚。MicroRNA（miRNA）通过导致目标mRNA的翻译抑制和/或降解来控制基因表达。OATP2B1 mRNA与蛋白表达之间没有显着相关性，表明转录后调控机制（例如miRNA）在OATP2B1表达的个体差异中起重要作用。在这个研究中，计算机分析表明，miR-24是调节OATP2B1表达的候选miRNA。据报道，miR-24降解HNF4αmRNA表达。我们发现，miR-24表达水平与人肝脏中OATP2B1 mRNA，蛋白质和HNF4αmRNA表达水平呈负相关。使用含有OATP2B1 3'非翻译区（3'UTR）或SLCO2B1启动子区的载体，miR-24前体的转染降低了转染细胞中的萤光素酶活性。在HepaRG细胞中，miR-24降低了OATP2B1和HNF4α的表达水平。这些结果表明，miR-24不仅通过HNF4αmRNA降解抑制OATP2B1的翻译，而且抑制OATP2B1的转录。
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