The Molecular Mechanisms Of The Expression Regulation Of HNF1α

Hepatocyte nuclear factors (HNFs) are transcription factors that regulate the expression of liver specific gene, and important for liver differentiation and metabolism. HNF1α, a pivotal member of the HNF gene family, regulates various genes related to liver functions and is indispensable to liver development. Our previous study showed that HNF1α can inhibited hepatocellular carcinoma (HCC) progress, up-regulate HNF1α can inhibite the proliferation of HCC cells. Animal experiments also indicated that HNFla suppressed the development of HCC. Though previous studies have revealed some mechanisms on HFN1α regulation, the detailed molecular mechanisms of the regulation of HNF1α expression has to be further improved. In this study, we have studied the regulation of HNF1α on transcriptional and post-translational level.Our study is based on the luciferase reporter system with the promoter or3’UTR of HNF1α. Useing targetscan softwares, we predict the potential transcription factors or microRNAs which may target the promoter or3’UTR of HNF1α. We find that there is a PAX6binding site on-197to-181region in HNF1α5’upstream, which can increase the transcription of HNF1α. And we also find two microRNA, hsa-mir-564and hsa-mir-665, which can target HNF1α3’UTR and decrease the expression of HNF1α. Moreover, we also show that TGF-β, the important cytokine of cancer development, can suppress the expression of HNFla mainly through the transcriptional regulation.