Identification and characterization of circRNAs as competing endogenous RNAs for miRNA-mRNA in colorectal cancer

PeerJ. 2019 Sep 19:7:e7602. doi: 10.7717/peerj.7602. eCollection 2019.

Abstract

Background: Recent studies showed that circRNAs are involved in the biological process of some human cancers. However, little is known about their functions in colorectal cancer (CRC).

Methods: Here we first revealed the expression profiles of circRNAs in the CRC tissues and the adjacent non-tumorous tissues using high-throughput sequencing. The sequence feature, chromosome location, alternative splicing and other characteristics of the circRNAs were also explored. The miRNA and mRNA expression profiles were then obtained by analyzing relevant CRC data retrived from the TCGA database. We obtained and analyzed the competing endogenous RNA (ceRNA) network of the top three pairs of the largest up-regulated and down-regulated circRNAs.

Results: In this study, we obtained 50,410 circRNAs in the CRC tissue and the adjacent non-tumor tissues, of which 33.7% (16,975) were new, and revealed differential changes in circRNA expression during colorectal carcinogenesis. We have identified six potential key circRNAs (circPIEZO1-3, hsa_circ_0067163, hsa_circ_0140188, hsa_circ_0002632, hsa_circ_0001998 and hsa_circ_0023990) associated with CRC, which play important roles in carcinogenesis as ceRNA for regulation of miRNA-mRNA network. In the subsequent KEGG analysis, several CRC-related pathways were found.

Conclusions: Our findings advance the understanding of the pathogenesis of CRC from the perspective of circRNAs and provide some circRNAs as candidate diagnostic biomarkers or potential therapeutic targets.

Keywords: CRC; High-throughput sequencing; TCGA; ceRNA network; circRNAs.

Grants and funding

This work was supported by the National Natural Science Foundation of China (61373057 to Xiaobo Li, 61775139 to Linhua Jiang), the Zhejiang Provincial Natural Science Foundation of China (LY17F020003 to Xiaobo Li), the Zhejiang Provincial Key Laboratory of Digital Design and Intelligent Manufacturing of Characteristic Cultural and Creative Products (2016E10007 to Xiaobo Li), the Shanghai Natural Science Foundation (15ZR1420800 to Sihua Peng), and the Jiaxing Municipal Science and Technology Project (2015AY23012 to Jingyu Wang). There was no additional external funding received for this study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.