The emerging roles of non-coding competing endogenous RNA in hepatocellular carcinoma
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Cancer Cell International Open Access
REVIEW
The emerging roles of non-coding competing endogenous RNA in hepatocellular carcinoma Gang Xu1†, Wei‑Yu Xu2†, Yao Xiao1†, Bao Jin1, Shun‑Da Du1* , Yi‑lei Mao1 and Zhong‑Tao Zhang2*
Abstract 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 vari‑ ous 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 biologi‑ cal 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. Keywords: Hepatocellular carcinoma, Noncoding RNA, Competing endogenous RNA Background Hepatocellular carcinoma (HCC), the most prevalent subtype of hepatic malignancy, is one of the leading causes of cancer-associated mortality worldwide [1]. There are an estimated 62 million new cases of HCC annually, 85% of which are diagnosed in developing *Correspondence: [email protected]; [email protected] † Gang Xu, Wei-Yu Xu and Yao Xiao contributed equally to this article. 1 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 2 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
countries [2]. Owing to the insidious symptoms and early metastases, most HCC patients are diagnosed at an advanced stage, leading to limited efficacy and even ineffectiveness of therapeutic approaches [3]. Despite continuous therapeutic advances, such as in surgical resection, liver transplantation and radiofrequency ablation
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