Transcriptome Profiling of Hepatocellular Carcinoma Uncovers Multi-Types of Dysregulated ncRNAs

Abstract

Transcriptome profiling of hepatocellular carcinoma (HCC) by next generation sequencing technology (NGS) has been broadly performed by previous researches, which facilitate our understanding of the molecular mechanisms of HCC formation, progression and metastasis. However, few studies jointly analyze multi-types of ncRNAs, including lncRNAs, circRNAs and miRNAs, and further uncover their implications in HCC. In this study, multi-types of ncRNAs were predicted and quantified based on RNA-seq data, and a large proportion of the novel circRNAs and miRNAs were validated in the independent dataset. Differential expression analysis characterized tumorigenesis- and subclass-associated ncRNAs and their potential biological function. Notably, the circRNA cZRANB1 and lncRNA DUXAP10 were also observed expressed higher in blood exosomes of HCC than healthy donors. Integrative analysis uncovers circRNA-miRNA, lncRNA-miRNA and competing endogenous RNA networks. Specifically, cZRANB1, LINC00501, CTD-2008L17.2, and SLC7A11-AS1 may function as ceRNAs that regulate mRNAs by competing the shared miRNAs. Further prognostic analysis demonstrated that the dysregulated ncRNAs had the potential to predict HCC patient's overall survival. Our systematic analysis provides not only rich data resources for related researchers, but also new insights into the molecular basis of how different ncRNAs coordinately or antagonistically participate into the pathogenesis process of diseases. Funding: This work was supported by the National High Technology Research and Development Program of China (2012AA020204, 2015AA020108), the China Human Proteomics Project (2014DFB30010, 2014DFB30030), National Science Foundation of China (31671377), Natural Science foundation of Shanghai (No.16ZR1429100).and Shanghai 111 Project (B14019). Declaration of Interest: The authors declare that they have no of interest. Ethical Approval: All procedures in the experiment were in agreement with the ethical principles. Patients involved in this study have been informed and signed consent before collection of samples, and the data (do not involve personal information) related to patients was completely anonymous.