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

Wenliang Yuan,Ye Wang,Jingyu Wang,Chaoxu Dai,Shouwen Jiang,Meiliang Wang,Xiaobo Li,Sihua Peng,Zhen Ye,Hao Xu,Dan Sun,Cai Wei,Linhua Jiang

doi:10.7717/peerj.7602

Abstract

BackgroundRecent 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).MethodsHere 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.ResultsIn 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.ConclusionsOur 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.

Highlights

Colorectal cancer (CRC) is a common malignant tumor of the digestive system in the world (1.4 million in 2012) (McGuire, 2016), and more than 50% of the patients eventually die from this disease
A total of 50,410 circRNAs derived from 9,620 host genes were identified in the human colorectal cancer (CRC) tissues and the adjacent non-tumorous tissues
By querying the clinical data in the TCGA database, we found that the expression levels of the six competing endogenous RNA (ceRNA)-related mRNAs significantly correlated to the survival time of the CRC patients (Fig. 4C), suggesting that circRNAs-selected may have prognostic value

Summary

Introduction

Colorectal cancer (CRC) is a common malignant tumor of the digestive system in the world (1.4 million in 2012) (McGuire, 2016), and more than 50% of the patients eventually die from this disease. Compared with other non-coding RNA molecules, such as miRNAs and lncRNAs, circRNAs have more desirable biomarker features, such as the stable circular structure, that can be used for disease diagnosis, for example atherosclerosis (Burd et al, 2010) and gastric cancer (Li et al, 2015). In CRC research, two recent studies demonstrated that circRNA_001569 and circular BANP modulate cell proliferation in colorectal cancer (Zhu et al, 2017; Xie et al, 2016). We first revealed the expression profiles of circRNAs in the CRC tissues and the adjacent non-tumorous tissues using high-throughput sequencing. 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. 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

Methods

Results

Discussion

Conclusion