The HNF1α-regulated lncRNA HNF1α-AS1 is Involved in the Regulation of Cytochrome P450 Expression in Human Liver Tissues and Huh7 Cells.

Expression of cytochrome P450s (CYPs) is regulated by epigenetic factors, such as DNA methylation, histone modifications, and non-coding RNAs through different mechanisms. Among these factors, long non-coding 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 CYP expression. The aim of this study was to explore the role of lncRNAs in the regulation of CYP 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 siRNAs or overexpression plasmids showed that HNF1α not only regulated the expression of HNF1α-AS1 and CYPs, but also regulated the expression of CAR, PXR, and aryl hydrocarbon receptor (AhR). In turn, HNF1α-AS1 regulated the expression of PXR and most CYPs without affecting the expression of HNF1α, AhR, and CAR. Moreover, the rifampicin-induced expression of CYPs 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 CYPs in the liver at both basal and drug-induced levels.