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Chen et al. Cancer Drug Resist 2024;7:9 Cancer
DOI: 10.20517/cdr.2023.151
Drug Resistance

Original Article Open Access

Circular RNA circNCOA3 promotes tumor
progression and anti-PD-1 resistance in colorectal

cancer

Dong-Liang Chen , Nuo Chen, Hui Sheng, Dong-Sheng Zhang
State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen
University Cancer Center, Guangzhou 510060, Guangdong, China.

Correspondence to: Prof. Dong-Liang Chen, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical
Research Center for Cancer, Sun Yat-sen University Cancer Center, No. 651 Dong Feng East Road, Guangzhou 510060,
Guangdong, China. E-mail: chendl@sysucc.org.cn
How to cite this article: Chen DL, Chen N, Sheng H, Zhang DS. Circular RNA circNCOA3 promotes tumor progression and anti-
PD-1 resistance in colorectal cancer. Cancer Drug Resist 2024;7:9. https://dx.doi.org/10.20517/cdr.2023.151
Received: 7 Dec 2023 First Decision: 1 Feb 2024 Revised: 8 Feb 2024 Accepted: 5 Mar 2024 Published: 13 Mar 2024

Academic Editor: Godefridus J. Peters Copy Editor: Pei-Yun Wang Production Editor: Pei-Yun Wang

Abstract
Aim: Circular RNAs (circRNAs) have been found to be involved in tumor progression, but their role in colorectal
cancer (CRC) immune escape remains to be elucidated.

Methods: circRNAs differentially expressed in responsive and resistant CRC tissues to programmed cell death 1
(PD-1) antibody therapy were identified by microarray analysis. The clinical and pathological significance of
circNCOA3 was validated in a separate cohort of CRC samples. The function of circNCOA3 was explored
experimentally. RNA immunoprecipitation and luciferase activity assays were conducted to identify downstream
targets of circNCOA3.
Results: The circNCOA3 was markedly overexpressed in CRC samples resistant to PD-1 blockade. circNCOA3
expression was significantly correlated with adverse tumor phenotypes and poor outcomes in CRC patients.
Knockdown of circNCOA3 expression markedly suppressed the proliferative and invasive capability of CRC cells.
+
Moreover, knockdown of circNCOA3 increased the proportion of CD8 T cells while decreasing the proportion of
myeloid-derived suppressor cells (MDSCs). Knockdown of circNCOA3 inhibited tumor growth and increased the
sensitivity to PD-1 antibody treatment in mouse tumor models. Further studies revealed that circNCOA3 acted as a
competing endogenous RNA (ceRNA) for miR-203a-3p.1 to influence the level of CXCL1.

© The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution 4.0
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