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

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

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