Comprehensive network analysis reveals alternative splicing-related lncRNAs in hepatocellular carcinoma

Wang, J., Wang, X., Bhat, A., Chen, Y., Xu, K., Mo, Y.-y., Yi, S. S. and Zhou, Y. (2020) Comprehensive network analysis reveals alternative splicing-related lncRNAs in hepatocellular carcinoma. Frontiers in Genetics, 11, 659. (doi: 10.3389/fgene.2020.00659) (PMID:32760422) (PMCID:PMC7373802)

Abstract

It is increasingly appreciated that long non-coding RNAs (lncRNAs) associated with alternative splicing (AS) could be involved in aggressive hepatocellular carcinoma. Although many recent studies show the alteration of RNA alternative splicing by deregulated lncRNAs in cancer, the extent to which and how lncRNAs impact alternative splicing at the genome scale remains largely elusive. We analyzed RNA-seq data obtained from 369 hepatocellular carcinomas (HCCs) and 160 normal liver tissues, quantified 198,619 isoform transcripts, and identified a total of 1,375 significant AS events in liver cancer. In order to predict novel AS-associated lncRNAs, we performed an integration of co-expression, protein-protein interaction (PPI) and epigenetic interaction networks that links lncRNA modulators (such as splicing factors, transcript factors, and miRNAs) along with their targeted AS genes in HCC. We developed a random walk-based multi-graphic (RWMG) model algorithm that prioritizes functional lncRNAs with their associated AS targets to computationally model the heterogeneous networks in HCC. RWMG shows a good performance evaluated by the ROC curve based on cross-validation and bootstrapping strategies. As a conclusion, our robust network-based framework has derived 31 AS-related lncRNAs that not only validates known cancer-associated cases MALAT1 and HOXA11-AS, but also reveals new players such as DNM1P35 and DLX6-AS1with potential functional implications. Survival analysis further provides insights into the clinical significance of identified lncRNAs.

• Item Type: Articles
• Additional Information: This study was supported by grants from the University of Mississippi Medical Center Intramural Research Support Program for Clinical Population Science fund (No. 51002630519 to YZ), the National Natural Science Foundation of China (No. 81602544 to JW), and the Shanghai Pujiang Talent Project (No. 18PJD029 to JW).
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Bhat, Dr Akshay
• Authors: Wang, J., Wang, X., Bhat, A., Chen, Y., Xu, K., Mo, Y.-y., Yi, S. S., and Zhou, Y.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
• Journal Name: Frontiers in Genetics
• Publisher: Frontiers Media
• ISSN: 1664-8021
• ISSN (Online): 1664-8021
• Copyright Holders: Copyright © 2020 Wang, Wang, Bhat, Chen, Xu, Mo, Yi and Zhou
• First Published: First published in Frontiers in Genetics 11:659
• Publisher Policy: Reproduced under a Creative Commons Licence