The HNF1α-Regulated LncRNA HNF1α-AS1 Is Involved in the Regulation of Cytochrome P450 Expression in Human Liver Tissues and Huh7 Cells
| العنوان: | The HNF1α-Regulated LncRNA HNF1α-AS1 Is Involved in the Regulation of Cytochrome P450 Expression in Human Liver Tissues and Huh7 Cells |
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| المؤلفون: | Liang Yan, Jingyang Liu, Xiao-bo Zhong, Pei Wang, Wei-hong Yang, Shitong Chen, Yali Nie, Shengna Han, Lirong Zhang, Guangming Liu, Yiting Wang, Liming Chen |
| المصدر: | Journal of Pharmacology and Experimental Therapeutics. 368:353-362 |
| بيانات النشر: | American Society for Pharmacology & Experimental Therapeutics (ASPET), 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 0301 basic medicine, Pharmacology, Regulation of gene expression, Pregnane X receptor, Biology, Aryl hydrocarbon receptor, digestive system, Cell biology, 03 medical and health sciences, Hepatocyte nuclear factors, 030104 developmental biology, 0302 clinical medicine, Constitutive androstane receptor, DNA methylation, Gene expression, biology.protein, Molecular Medicine, Epigenetics, 030217 neurology & neurosurgery |
| الوصف: | Expression of cytochrome P450s (P450s) is regulated by epigenetic factors, such as DNA methylation, histone modifications, and noncoding RNAs through different mechanisms. Among these factors, long noncoding RNAs (lncRNAs) have been shown to play important roles in the regulation of gene expression; however, little is known about the effects of lncRNAs on the regulation of P450 expression. The aim of this study was to explore the role of lncRNAs in the regulation of P450 expression by using human liver tissues and hepatoma Huh7 cells. Through lncRNA microarray analysis and quantitative polymerase chain reaction in human liver tissues, we found that the lncRNA hepatocyte nuclear factor 1 alpha antisense 1 (HNF1α-AS1), an antisense RNA of HNF1α, is positively correlated with the mRNA expression of CYP2C8, 2C9, 2C19, 2D6, 2E1, and 3A4 as well as pregnane X receptor (PXR) and constitutive androstane receptor (CAR). Gain- and loss-of-function studies in Huh7 cells transfected with small interfering RNAs or overexpression plasmids showed that HNF1α not only regulated the expression of HNF1α-AS1 and P450s, but also regulated the expression of CAR, PXR, and aryl hydrocarbon receptor (AhR). In turn, HNF1α-AS1 regulated the expression of PXR and most P450s without affecting the expression of HNF1α, AhR, and CAR. Moreover, the rifampicin-induced expression of P450s was also affected by HNF1α and HNF1α-AS1. In summary, the results of this study suggested that HNF1α-AS1 is involved in the HNF1α-mediated regulation of P450s in the liver at both basal and drug-induced levels. |
| تدمد: | 1521-0103 0022-3565 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::fa4ff2bb6274cb47be10d1103334c78c https://doi.org/10.1124/jpet.118.252940 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi...........fa4ff2bb6274cb47be10d1103334c78c |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15210103 00223565 |
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