Xu Gang, Xu Wei-Yu, Xiao Yao, Jin Bao, Du Shun-Da, Mao Yi-Lei, Zhang Zhong-Tao
Department of Liver Surgery, Peking Union Medical College (PUMC) Hospital and Chinese Academy of Medical Sciences, 1# Shuaifuyuan, Wangfujing, Dong-Cheng District, Beijing, 100730 China.
Department of General Surgery, Beijing Friendship Hospital, Capital Medical University; Beijing Key Laboratory of Cancer Invasion and Metastasis Research & National Clinical Research Center for Digestive Diseases, No. 95 Yong-An Road, Xi-Cheng District, Beijing, 100050 People's Republic of China.
Cancer Cell Int. 2020 Oct 12;20:496. doi: 10.1186/s12935-020-01581-5. eCollection 2020.
Accumulating evidence has emerged revealing that noncoding RNAs (ncRNAs) play essential roles in the occurrence and development of hepatocellular carcinoma (HCC). However, the complicated regulatory interactions among various ncRNAs in the development of HCC are not entirely understood. The newly discovered mechanism of competing endogenous RNAs (ceRNAs) uncovered regulatory interactions among different varieties of RNAs. In recent years, a growing number of studies have suggested that ncRNAs, including long ncRNAs, circular RNAs and pseudogenes, play major roles in the biological functions of the ceRNA network in HCC. These ncRNAs can share microRNA response elements to affect microRNA affinity with target RNAs, thus regulating gene expression at the transcriptional level and both physiological and pathological processes. The ncRNAs that function as ceRNAs are involved in diverse biological processes in HCC cells, such as tumor cell proliferation, epithelial-mesenchymal transition, invasion, metastasis and chemoresistance. Based on these findings, ncRNAs that act as ceRNAs may be promising candidates for clinical diagnosis and treatments. In this review, we discuss the mechanisms and research methods of ceRNA networks. We also reviewed the recent advances in studying the roles of ncRNAs as ceRNAs in HCC and highlight possible directions and possibilities of ceRNAs as diagnostic biomarkers or therapeutic targets. Finally, the limitations, gaps in knowledge and opportunities for future research are also discussed.
越来越多的证据表明，非编码RNA（ncRNAs）在肝细胞癌（HCC）的发生和发展中起重要作用。然而，HCC发生过程中各种ncRNAs之间复杂的调控相互作用尚未完全明了。新发现的竞争性内源RNA（ceRNAs）机制揭示了不同种类RNA之间的调控相互作用。近年来，越来越多的研究表明，包括长链ncRNAs、环状RNAs和假基因在内的ncRNAs在HCC的ceRNA网络生物学功能中起主要作用。这些ncRNAs可以共享微小RNA反应元件，影响微小RNA与靶RNA的亲和力，从而在转录水平以及生理和病理过程中调节基因表达。作为ceRNAs发挥作用的ncRNAs参与HCC细胞的多种生物学过程，如肿瘤细胞增殖、上皮-间质转化、侵袭、转移和化疗耐药性。基于这些发现，作为ceRNAs的ncRNAs可能是临床诊断和治疗的有希望的候选者。在本综述中，我们讨论了ceRNA网络的机制和研究方法。我们还综述了近年来关于ncRNAs作为ceRNAs在HCC中的作用的研究进展，并强调了ceRNAs作为诊断生物标志物或治疗靶点的可能方向和可能性。最后，还讨论了局限性、知识空白和未来研究的机会。
