RNA-Seq profiling of circular RNAs in human colorectal cancer 5-fluorouracil resistance and potential biomarkers

doi:10.4251/wjgo.v14.i3.678

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World Journal of Gastrointestinal Oncology

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World J Gastrointest Oncol. Mar 15, 2022; 14(3): 678-689
Published online Mar 15, 2022. doi: 10.4251/wjgo.v14.i3.678

RNA-Seq profiling of circular RNAs in human colorectal cancer 5-fluorouracil resistance and potential biomarkers

Pei-Qiu Cheng, Yu-Jing Liu, Sheng-An Zhang, Lu Lu, Wen-Jun Zhou, Dan Hu, Han-Chen Xu, Guang Ji

Pei-Qiu Cheng, Yu-Jing Liu, Lu Lu, Wen-Jun Zhou, Han-Chen Xu, Guang Ji, Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China

Sheng-An Zhang, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China

Dan Hu, Shanghai Pudong New Area Hospital of Traditional Chinese Medicine, Shanghai 200032, China

Author contributions: Cheng PQ and Liu YJ contributed equally to this work, they performed the majority of the experiments and analyzed the data; Lu L and Zhang SA contributed to the analysis of sequencing data and network prediction; Zhou WJ and Hu D coordinated the research; Ji G and Xu HC are co-corresponding authors, and they contributed to the design of the study and editing the manuscript; all authors read, and approved the final manuscript.

Supported by National Natural Science Foundation of China, No. 81874206; Shanghai Rising-Star Program, No. 20QA1409300; and the Program for Young Eastern Scholar at Shanghai Institutions of Higher Learning, No. QD2019034.

Institutional review board statement: This study did not involve a clinical case study.

Conflict-of-interest statement: No conflict of interest.

Data sharing statement: The datasets used during the current study were available from the corresponding authors on reasonable request.

Corresponding author: Guang Ji, MD, PhD, Chief Doctor, Professor, Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, No. 725 South Wanping Road, Shanghai 200032, China. jiliver@vip.sina.com

Received: July 28, 2021
Peer-review started: July 28, 2021
First decision: September 5, 2021
Revised: September 10, 2021
Accepted: January 22, 2022
Article in press: January 22, 2022
Published online: March 15, 2022
Processing time: 225 Days and 4 Hours

Abstract

BACKGROUND

Colorectal cancer (CRC) is a commonly diagnosed cancer of the digestive system worldwide. Although chemotherapeutic agents and targeted therapeutic drugs are currently available for CRC treatment, drug resistance is a problem that cannot be ignored and needs to be solved.

AIM

To explore the relationship between circular RNA (circRNA) and CRC drug resistance. circRNA plays a key role in the occurrence and development of cancers, but its function in the process of drug resistance has not been widely revealed.

METHODS

To explore the role of circRNA in 5-fluorouracil (5-Fu) resistance, we performed the circRNA expression profile in two CRC cell lines and their homologous 5-Fu resistant cells by high-throughput sequencing.

RESULTS

We validated the differentially expressed circRNAs in other two paired CRC cells, confirmed that circ_0002813 and circ_0000236 could have a potential competitive endogenous RNA mechanism and be involved in the formation of 5-Fu resistance. And we combined the sequencing results of mRNA to construct the regulatory network of circRNA-miRNA-mRNA.

CONCLUSION

Our study revealed that circ_0002813 and circ_0000236 may as the biomarkers to predict the occurrence of 5-Fu resistance in CRC.

Keywords: Colorectal cancer; 5-Fluorouracil resistance; Circular RNAs; RNA sequencing; Network prediction; Biomarkers

Core Tip: Therapy resistance has been a culprit for colorectal cancer (CRC) treatment. 5-fluorouracil is a first-line chemotherapeutic agent for CRC, and it is very important to reveal the potential biomarkers and mechanisms of resistance. Circular RNA (circRNA) plays a key role in the occurrence and development of cancers, but its function in the process of drug resistance has not been widely revealed. In this study, through the construction of drug-resistant cell lines and high-throughput sequencing technology, we revealed the changes in the expression of circRNAs during the process of drug resistance, and searched for circRNAs that could predict the occurrence of drug resistance as potential biomarkers.