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Targeting H19, an Imprinted Long Non-Coding RNA, in Hepatic Functions and Liver Diseases
Chad Pope1, Shashank Mishra2, Joshua Russell3
1Department of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut, 69 N Eagleville Road, Storrs, CT 06269, USA. chad.pope@uconn.edu.
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.
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