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靶向印记长链非编码RNA H19在肝脏功能和肝脏疾病中的作用

Targeting H19, an Imprinted Long Non-Coding RNA, in Hepatic Functions and Liver Diseases.

作者信息

Pope Chad, Mishra Shashank, Russell Joshua, Zhou Qingqing, Zhong Xiao-Bo

机构信息

Department of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut, 69 N Eagleville Road, Storrs, CT 06269, USA.

Department of Physiology and Neurobiology, University of Connecticut, 75 N Eagleville Road, Storrs, CT 06269, USA.

出版信息

Diseases. 2017 Mar 8;5(1):11. doi: 10.3390/diseases5010011.

Abstract

H19 is a long non-coding RNA regulated by genomic imprinting through methylation at the locus between H19 and IGF2. H19 is important in normal liver development, controlling proliferation and impacting genes involved in an important network controlling fetal development. H19 also plays a major role in disease progression, particularly in hepatocellular carcinoma. H19 participates in the epigenetic regulation of many processes impacting diseases, such as activating the miR-200 pathway by histone acetylation to inhibit the epithelial-mesenchymal transition to suppress tumor metastasis. Furthermore, H19's normal regulation is disturbed in diseases, such as hepatocellular carcinoma. In this disease, aberrant epigenetic maintenance results in biallelic expression of IGF2, leading to uncontrolled cellular proliferation. This review aims to further research utilizing H19 for drug discovery and the treatment of liver diseases by focusing on both the epigenetic regulation of H19 and how H19 regulates normal liver functions and diseases, particularly by epigenetic mechanisms.

摘要

H19是一种长链非编码RNA,通过H19与IGF2之间位点的甲基化受基因组印记调控。H19在正常肝脏发育中很重要,可控制细胞增殖并影响参与胎儿发育重要网络的基因。H19在疾病进展中也起主要作用,尤其是在肝细胞癌中。H19参与影响疾病的许多过程的表观遗传调控,例如通过组蛋白乙酰化激活miR-200途径以抑制上皮-间质转化,从而抑制肿瘤转移。此外,H19的正常调控在疾病(如肝细胞癌)中受到干扰。在这种疾病中,异常的表观遗传维持导致IGF2的双等位基因表达,从而导致细胞增殖失控。本综述旨在通过关注H19的表观遗传调控以及H19如何调节正常肝脏功能和疾病,特别是通过表观遗传机制,进一步研究利用H19进行药物发现和治疗肝脏疾病。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37b5/5456333/3c869ac932a5/diseases-05-00011-g001.jpg

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