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Molecular Cancer
Published in: Molecular Cancer 1/2021

Open Access 01-12-2021 | Gastric Cancer | Research

The circular RNA circDLG1 promotes gastric cancer progression and anti-PD-1 resistance through the regulation of CXCL12 by sponging miR-141-3p

Authors: Dong-Liang Chen, Hui Sheng, Dong-Sheng Zhang, Ying Jin, Bai-Tian Zhao, Nuo Chen, Kang Song, Rui-Hua Xu

Published in: Molecular Cancer | Issue 1/2021

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Abstract

Background

Dysregulation of circular RNAs (circRNAs) plays an important role in the development of gastric cancer; thus, revealing the biological and molecular mechanisms of abnormally expressed circRNAs is critical for identifying novel therapeutic targets in gastric cancer.

Methods

A circRNA microarray was performed to identify differentially expressed circRNAs between primary and distant metastatic tissues and between gastric cancer tissues sensitive or resistant to anti-programmed cell death 1 (PD-1) therapy. The expression of circRNA discs large homolog 1 (DLG1) was determined in a larger cohort of primary and distant metastatic gastric cancer tissues. The role of circDLG1 in gastric cancer progression was evaluated both in vivo and in vitro, and the effect of circDLG1 on the antitumor activity of anti-PD-1 was evaluated in vivo. The interaction between circDLG1 and miR-141-3p was assessed by RNA immunoprecipitation and luciferase assays.

Results

circDLG1 was significantly upregulated in distant metastatic lesions and gastric cancer tissues resistant to anti-PD-1 therapy and was associated with an aggressive tumor phenotype and adverse prognosis in gastric cancer patients treated with anti-PD-1 therapy. Ectopic circDLG1 expression promoted the proliferation, migration, invasion, and immune evasion of gastric cancer cells. Mechanistically, circDLG1 interacted with miR-141-3p and acted as a miRNA sponge to increase the expression of CXCL12, which promoted gastric cancer progression and resistance to anti-PD-1-based therapy.

Conclusions

Overall, our findings demonstrate how circDLG1 promotes gastric cancer cell proliferation, migration, invasion and immune evasion and provide a new perspective on the role of circRNAs during gastric cancer progression.
Appendix
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Metadata
Title
The circular RNA circDLG1 promotes gastric cancer progression and anti-PD-1 resistance through the regulation of CXCL12 by sponging miR-141-3p
Authors
Dong-Liang Chen
Hui Sheng
Dong-Sheng Zhang
Ying Jin
Bai-Tian Zhao
Nuo Chen
Kang Song
Rui-Hua Xu
Publication date
01-12-2021
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2021
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/s12943-021-01475-8

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