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Abstract Details
Alternative Splicing in Hepatocellular Carcinoma
Cell Mol Gastroenterol Hepatol. 2020 May 8;S2352-345X(20)30068-0.doi: 10.1016/j.jcmgh.2020.04.018. Online ahead of print.
Seung Eun Lee1, Karel P Alcedo2, Hong Jin Kim3, Natasha T Snider4
Author information
1Department of Surgery, Chung-Ang University, Seoul, Korea; Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
2Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
3Department of Surgery, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
4Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina. Electronic address: ntsnider@med.unc.edu.
Free article
Abstract
Hepatocellular carcinoma (HCC) accounts for the majority of primary liver cancer cases, with more than 850,000 new diagnoses per year globally. Recent trends in the United States have shown that liver cancer mortality has continued to increase in both men and women, while 5-year survival remains less than 20%. Understanding key mechanisms that drive chronic liver disease progression to HCC can show new therapeutic targets and biomarkers for early detection of HCC. In that regard, many studies have underscored the importance of alternative splicing as a source of novel HCC prognostic markers and disease targets. Alternative splicing of RNA provides functional diversity to the genome, and endows cells with the ability to rapidly remodel the proteome. Genes that control fundamental processes, such as metabolism, cell proliferation, and apoptosis, are altered globally in HCC by alternative splicing. This review highlights the major splicing factors, RNA binding proteins, transcriptional targets, and signaling pathways that are of key relevance to HCC. We highlight primary research from the past 3-5 years involving functional interrogation of alternative splicing in rodent and human liver, using both large-scale transcriptomic and focused mechanistic approaches. Because this is a rapidly advancing field, we anticipate that it will be transformative for the future of basic liver biology, as well as HCC diagnosis and management.