J Cancer 2019; 10(15):3361-3372. doi:10.7150/jca.31243

Research Paper

Circular RNA Signature in Hepatocellular Carcinoma

Lipeng Qiu1✉, Tao Wang1, Qi Ge1, Han Xu2, Yihang Wu3, Qi Tang1, Keping Chen1✉

1. Institute of Life Sciences, Jiangsu University, Zhenjiang 212013, Jiangsu, China
2. School of Pharmacy, Jiangsu University, Zhenjiang, Jiangsu Province, 212013, China.
3. Department of Pharmacy, College of Life Sciences, China Jiliang University, Hangzhou 310018, Zhejiang, China

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Citation:
Qiu L, Wang T, Ge Q, Xu H, Wu Y, Tang Q, Chen K. Circular RNA Signature in Hepatocellular Carcinoma. J Cancer 2019; 10(15):3361-3372. doi:10.7150/jca.31243. Available from http://www.jcancer.org/v10p3361.htm

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Abstract

Hepatocellular carcinoma (HCC) is one of the most common cancers in the world. Circular RNAs (circRNAs) are a new class of endogenous functional non-coding RNAs (ncRNAs), and have been demonstrated to play important roles in the development of HCC. This study aimed to explore the significance of circRNAs in HCC progression. HCC-associated circRNA expression profiles GSE94508 and GSE97332 were downloaded from the Gene Expression Omnibus database (GEO), and 87 differentially expressed circRNAs (DECs) between HCC tissues and paired non-cancer tissues were identified, including 76 up-regulated and 11 down-regulated circRNAs. Gene ontolog (GO) and pathway analyses of the host genes of these DECs suggested that these host genes were enriched in cell adhesion, cytosol, and protein binding, and were associated with tight junction and Wnt signaling pathways. CircRNA-miRNA interaction prediction identified 20 miRNAs that predispose to interact with DECs. Among these, four essential miRNAs, hsa-miR-7-5p, hsa-miR-145-5p, hsa-miR-203a-3p, and hsa-miR-192-5p, were reported to play pivotal roles in HCC progression by targeting multiple genes. Pathway analysis suggested that putative target genes of these essential miRNAs were involved in HCC-associated signaling pathways, such as Wnt, TGF-β, and Ras; whereas protein-protein network (PPI) analysis demonstrated that some validated target genes of these miRNAs, such as PIK3CA, AKT1, MYC, JUN, SMAD4, and SRC, were hub target genes as they have more counts of interacting protein. In the meantime, the deregulation of some DECs was validated in HCC cell line HepG2 compared with normal liver cell line L02 by quantitative real-time polymerase chain reaction (qRT-PCR) and the Sanger sequencing. This study identified a set of DECs in HCC, and provided a comprehensive understanding of the roles of these DECs in HCC progression.

Keywords: circular RNA, miRNA sponge, hepatocellular carcinoma, bioinformatic analysis