Clinical and Translational Research
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Apr 16, 2022; 10(11): 3352-3368
Published online Apr 16, 2022. doi: 10.12998/wjcc.v10.i11.3352
Identification of circ_0000375 and circ_0011536 as novel diagnostic biomarkers of colorectal cancer
Teng-Fei Yin, Shi-Yu Du, Dong-Yan Zhao, Xi-Zhen Sun, Yuan-Chen Zhou, Qian-Qian Wang, Ge-Yu-Jia Zhou, Shu-Kun Yao
Teng-Fei Yin, Shi-Yu Du, Yuan-Chen Zhou, Qian-Qian Wang, Shu-Kun Yao, Graduate School, Peking University China-Japan Friendship School of Clinical Medicine, Beijing 100029, China
Shi-Yu Du, Dong-Yan Zhao, Ge-Yu-Jia Zhou, Shu-Kun Yao, Department of Gastroenterology, China-Japan Friendship Hospital, Beijing 100029, China
Dong-Yan Zhao, Xi-Zhen Sun, Ge-Yu-Jia Zhou, Graduate School, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China
Xi-Zhen Sun, Department of Gastroenterology, Beijing Jishuitan Hospital, Beijing 100035, China
Author contributions: Yin TF conceived and designed the study, performed sample collection and formal analysis, and prepared the original draft; Du SY, Zhao DY and Sun XZ participated in sample acquisition, data analysis and manuscript revision; Zhou YC, Wang QQ and Zhou GYJ 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 the 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.
Informed consent statement: All participants signed written informed consent.
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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Shu-Kun Yao, MD, PhD, Doctor, 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: October 29, 2021
Peer-review started: October 29, 2021
First decision: December 27, 2021
Revised: December 30, 2021
Accepted: February 12, 2022
Article in press: February 12, 2022
Published online: April 16, 2022
Processing time: 161 Days and 5.7 Hours
ARTICLE HIGHLIGHTS
Research background

Colorectal cancer (CRC) is a common tumor worldwide. Circular ribonucleic acids (circRNAs) have been reported to regulate CRC as microRNA (miRNA) sponges. However, the aberrant expression and biological functions of circRNAs in CRC remain to be further explored.

Research motivation

CircRNAs might serve as novel biomarker candidates for CRC diagnosis. Further exploration of useful biomarkers to improve CRC diagnosis and treatment is crucial.

Research objectives

This study aimed to identify circRNAs that could be potential biomarkers of CRC and explore their functions in CRC carcinogenesis.

Research methods

Cir_0000375 and circ_0011536 were selected as CRC biomarker candidates using the Gene Expression Omnibus (GEO) database. Quantitative real-time polymerase chain reaction was utilized to evaluate the expression levels of these 2 circRNAs in CRC tissues, serum samples and cell lines. Functional experiments, including cell counting kit-8 (CCK-8), wound healing and Transwell invasion assays, were carried out after overexpression of cir_0000375 and circ_0011536 in CRC cell lines. Furthermore, the expression levels of target miRNAs in CRC tissues were explored in GEO datasets and CRC cell lines. Then, the interactions of circRNAs and miRNAs and enrichment analysis of the miRNAs and target genes were further performed.

Research results

Our findings demonstrated that circ_0000375 and circ_0011536 were downregulated in CRC cell lines, tissues and serum samples and showed good diagnostic performance. Furthermore, these 2 circRNAs significantly inhibited CRC cell proliferation, migration and invasion. As potential targets of circ_0000375 and circ_0011536, miR-1182 and miR-1246, respectively, were overexpressed in CRC cells and tissues.

Research conclusions

Circ_0000375 and circ_0011536 may function as tumor suppressors and serve as novel biomarkers for CRC diagnosis and are promising candidates for therapeutic exploration.

Research perspectives

Our findings uncover the mechanisms by which 2 circRNAs, circ_0000375 and circ_0011536, suppress CRC cell growth and progression and provide novel diagnostic biomarkers and promising therapeutic targets for CRC.