Basic Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Jun 26, 2021; 9(18): 4520-4541
Published online Jun 26, 2021. doi: 10.12998/wjcc.v9.i18.4520
Identification of the circRNA-miRNA-mRNA regulatory network and its prognostic effect in colorectal cancer
Teng-Fei Yin, Dong-Yan Zhao, Yuan-Chen Zhou, Qian-Qian Wang, Shu-Kun Yao
Teng-Fei Yin, Yuan-Chen Zhou, Qian-Qian Wang, Shu-Kun Yao, Graduate school, Peking University China-Japan Friendship School of Clinical Medicine, Beijing 100029, China
Dong-Yan Zhao, Graduate School, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China
Dong-Yan Zhao, Shu-Kun Yao, Department of Gastroenterology, China-Japan Friendship Hospital, Beijing 100029, China
Author contributions: Yin TF conceived and designed the study, performed formal analysis and prepared the original draft; Zhao DY participated in data analysis and manuscript revision; Zhou YC and Wang QQ reviewed and edited the manuscript critically; Yao SK designed and supervised the study, revised the manuscript, and obtained the funding; all authors read and approved the final manuscript.
Supported by National Key Development Plan for Precision Medicine Research, No. 2017YFC0910002.
Institutional review board statement: This study was approved by the Ethics Committee of China-Japan Friendship Hospital, No. 2018-116-K85-1.
Conflict-of-interest statement: There are no conflicts of interest to report.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Shu-Kun Yao, MD, PhD, Professor, Graduate School, Peking University China-Japan Friendship School of Clinical Medicine, No. 2 Yinghua East Road, Chaoyang District, Beijing 100029, China. shukunyao@126.com
Received: December 11, 2020
Peer-review started: December 11, 2020
First decision: January 17, 2021
Revised: January 26, 2021
Accepted: February 26, 2021
Article in press: February 26, 2021
Published online: June 26, 2021
Processing time: 182 Days and 0.5 Hours
ARTICLE HIGHLIGHTS
Research background

Colorectal cancer (CRC) is one of the most common malignant tumors worldwide. Circular RNA (circRNA) and microRNA (miRNA), acting as competing endogenous RNAs (ceRNAs), have been investigated to play vital roles in carcinogenesis. Accumulating evidence highlights that it is necessary to further explore the biological function of circRNA and miRNA in CRC pathogenesis and prognosis.

Research motivation

Dysregulated circRNAs, miRNAs and mRNAs could closely associate with the progression and prognosis of CRC and act as potential CRC-specific predictors, but the competitive regulatory pattern and biological function mechanism among circRNAs, miRNAs and mRNAs are still complicated and have not yet been elucidated.

Research objectives

This study aimed to uncover a CRC-specific competitive regulatory model among circRNAs, miRNAs and mRNAs and explore the subnetwork associated with CRC prognosis.

Research methods

Expression profiles of circRNAs, miRNAs and mRNAs were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed (DE) circRNAs, miRNAs and mRNAs in CRC tissues and the predicted target molecules of circRNAs and miRNAs were intersected to obtain a CRC-specific ceRNA network. GO and KEGG pathway analyses were conducted to explore the mechanism of CRC pathogenesis. Based on the survival analysis using the gene profiles and clinical information in The Cancer Genome Atlas (TCGA) database, the mRNAs significantly associated with the clinical outcome of CRC patients were identified and a prognostic subnetwork was constructed.

Research results

There were 55 DEcircRNAs, 114 DEmiRNAs and 267 DEmRNAs of CRC in three datasets (GSE126095, GSE41655 and GSE41657) from GEO database. After intersected with predicted targets, 19 circRNAs, 13 miRNAs and 28 mRNAs were chosen to develop ceRNA network. Go and KEGG analyses indicated that several signaling pathways might participate in the tumorigenesis. After verifying effect in TCGA database by survival analysis, we finally recognized 3 mRNAs (CA2, ITLN1 and LRRC19) associated with prognosis, and constructed a ceRNA subnetwork including 5 circRNAs (hsa_circ_0080210, hsa_circ_0007158, hsa_circ_0000375, hsa_circ_0018909 and hsa_circ_0011536) and 3 miRNAs (hsa-miR-601, hsa-miR-671-5p and hsa-miR-765).

Research conclusions

A circRNA-miRNA-mRNA regulatory network closely associated with the progression and clinical outcome of CRC was identified, which might include promising biomarkers for carcinogenesis and therapeutic targets.

Research perspectives

We have provided a deeper understanding of the circRNA-related ceRNA mechanism of CRC by developing a circRNA-miRNA-mRNA regulatory network. Comprehensive experimental studies are still required to confirm our findings and provide new opportunities for targeted therapeutics.