Non-coding RNAs in hepatocellular carcinoma: molecular functions and pathological implications

• Published in: Nature reviews. Gastroenterology & hepatology Vol. 15; no. 3; pp. 137 - 151
• Main Authors: Wong, Chun-Ming, Tsang, Felice Ho-Ching, Ng, Irene Oi-Lin
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.03.2018; Nature Publishing Group
• Subjects: 631/337/176; 631/337/384; 631/337/384/331; 692/4020/4021/1607/1610; Biomedicine; Carcinogenesis; Care and treatment; Deoxyribonucleic acid; Development and progression; DNA; Gastroenterology; Gene expression; Gene regulation; Genetic aspects; Health aspects; Hepatocellular carcinoma; Hepatology; Hepatoma; Liver cancer; Malignancy; Medicine & Public Health; Mesenchyme; Metastases; MicroRNAs; miRNA; Molecular modelling; Next-generation sequencing; Oncogenes; Post-transcription; review-article; Therapeutic applications; Transcription activation; Tumors
• ISSN: 1759-5045; 1759-5053; 1759-5053
• DOI: 10.1038/nrgastro.2017.169

Key Points Protein-coding sequence accounts for only 2% of the human genome, with the function of the remaining 98% of non-coding sequences in the human genome being largely elusive A large number of small and long non-coding RNAs (ncRNAs) have been identified, and deregulation of ncRNAs has a critical role in liver carcinogenesis MicroRNAs negatively regulate gene expression at the post-transcriptional level; microRNAs can function as an 'oncomiRs' to repress tumour-suppressor genes or, vice versa, can act as a tumour suppressor to counteract oncogenes Long ncRNAs belong to functionally divergent groups of ncRNAs that regulate gene expression and other molecular functions through interacting with DNA, RNA and proteins Deregulation of ncRNAs profoundly contributes to liver carcinogenesis of diverse aetiologies, liver cancer stem cell formation, hepatocellular carcinoma epigenetic reprogramming and cancer metastasis Non-coding RNAs are potential molecular markers and therapeutic targets of human hepatocellular carcinoma A growing body of evidence implicates non-coding RNAs (ncRNAs) in liver carcinogenesis. In this Review, the authors summarize the pathological roles of ncRNAs in hepatocellular carcinoma and explore the potential applications of ncRNAs as diagnostic tools and therapeutic targets. Hepatocellular carcinoma (HCC) is a leading lethal malignancy worldwide. However, the molecular mechanisms underlying liver carcinogenesis remain poorly understood. Over the past two decades, overwhelming evidence has demonstrated the regulatory roles of different classes of non-coding RNAs (ncRNAs) in liver carcinogenesis related to a number of aetiologies, including HBV, HCV and NAFLD. Among the ncRNAs, microRNAs, which belong to a distinct class of small ncRNAs, have been proven to play a crucial role in the post-transcriptional regulation of gene expression. Deregulation of microRNAs has been broadly implicated in the inactivation of tumour-suppressor genes and activation of oncogenes in HCC. Modern high-throughput sequencing analyses have unprecedentedly identified a very large number of non-coding transcripts. Divergent groups of long ncRNAs have been implicated in liver carcinogenesis through interactions with DNA, RNA or proteins. Overall, ncRNAs represent a burgeoning field of cancer research, and we are only beginning to understand the importance and complicity of the ncRNAs in liver carcinogenesis. In this Review, we summarize the common deregulation of small and long ncRNAs in human HCC. We also comprehensively review the pathological roles of ncRNAs in liver carcinogenesis, epithelial-to-mesenchymal transition and HCC metastasis and discuss the potential applications of ncRNAs as diagnostic tools and therapeutic targets in human HCC.