Department of Pathology, The University of Hong Kong, Block T, Queen Mary Hospital, Pokfulam, Hong Kong.
State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong Jockey Club Building for Interdisciplinary Research, Hong Kong, Pokfulam, Hong Kong.
Nat Rev Gastroenterol Hepatol. 2018 Mar;15(3):137-151. doi: 10.1038/nrgastro.2017.169. Epub 2018 Jan 10.
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.
肝细胞癌（HCC）是全球主要的致命恶性肿瘤。然而，肝发生致癌的分子机制仍知之甚少。在过去的二十年中，大量证据表明，不同种类的非编码 RNA（ncRNA）在与多种病因（包括 HBV、HCV 和 NAFLD）相关的肝发生致癌中发挥着调节作用。在 ncRNA 中，miRNAs 属于一类独特的小 ncRNA，已被证明在基因表达的转录后调控中发挥着关键作用。miRNAs 的失调广泛涉及 HCC 中肿瘤抑制基因的失活和癌基因的激活。现代高通量测序分析前所未有地鉴定出大量的非编码转录本。长 ncRNA 的不同群体通过与 DNA、RNA 或蛋白质的相互作用被牵涉到肝发生致癌中。总的来说，ncRNA 代表了癌症研究的一个新兴领域，我们才刚刚开始理解 ncRNA 在肝发生致癌中的重要性和复杂性。在这篇综述中，我们总结了人类 HCC 中小 ncRNA 和长 ncRNA 的常见失调。我们还全面综述了 ncRNA 在肝发生致癌、上皮-间充质转化和 HCC 转移中的病理作用，并讨论了 ncRNA 作为人类 HCC 诊断工具和治疗靶点的潜在应用。
