Transcriptome-Wide Analysis Reveals the Landscape of Aberrant Alternative Splicing Events in Liver Cancer

Hepatology : Official Journal of the American Association for the Study of Liver Diseases
Shengli LiXianghuo He

Abstract

Alternative splicing (AS) is assumed to be a pivotal determinant for the generation of diverse transcriptional variants in cancer. However, the comprehensive dysregulation of AS and the prospective biological and clinical relevance in hepatocellular carcinoma (HCC) remain obscure. Here, we identified and depicted the AS landscape in HCC by performing reference-based assembly of sequencing reads from over 600 RNA sequencing (RNA-seq) libraries. We detected various differentially spliced ASEs across patients covering not only protein-coding genes, but also considerable numbers of noncoding genes. Strikingly, alternative transcription initiation was found to frequently occur in HCC. These differential ASEs were highly related to "cancer hallmarks" and involved in metabolism-related pathways in particular. In addition, 243 differential ASEs were identified as risk predictors for HCC patient survival. The isoform switch of metabolism-related gene UGP2 (UDP-glucose pyrophosphorylase 2) might play an essential role in HCC. We further constructed regulatory networks between RNA-binding protein (RBP) genes and the corresponding ASEs. Further analysis demonstrated that the regulated networks were enriched in a variety of metabolism-relat...Continue Reading

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Citations

Jul 14, 2019·The Journal of Pathology·Hoin KangWook Kim
Oct 3, 2020·Journal of Cellular and Molecular Medicine·Zheng ZhaoFan Wu
Apr 4, 2019·BMC Genomics·Alberto Berral-GonzalezGuillermo Ayala
Jan 27, 2019·Journal of Cellular Physiology·Dan SuYandong Zhang
Jan 12, 2021·Computational and Structural Biotechnology Journal·Wei Jiang, Liang Chen
Mar 6, 2021·Frontiers in Cell and Developmental Biology·Wei HuShengli Li
Mar 16, 2021·Frontiers in Endocrinology·Panyisha WuNicholas J G Webster
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Jan 7, 2020·Molecular Therapy. Nucleic Acids·Sheng ShenJiwei Zhang
Oct 10, 2021·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Hong-Zhong ZhouJuan Chen
Jan 18, 2022·BMC Cancer·Tamara BabicAleksandra Nikolic

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