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DNMT1对ECRG4的下调通过IRF3/IFN-γ/miR-29b/DNMT1/ECRG4正反馈环促进子宫内膜癌生长。

Downregulation of ECRG4 by DNMT1 promotes EC growth via IRF3/IFN-γ/miR-29b/DNMT1/ECRG4 positive feedback loop.

作者信息

Yang Ke, Chai Shuaining, Song Helong, Cao Sinan, Gao Fangmiao, Zhou Chenxuan, Li Linwei

机构信息

Department of Oncology, Zhengzhou University People's Hospital, Henan Provincial People's Hospital, Zhengzhou, 450003 Henan, China.

Department of Oncology, Henan University People's Hospital, Henan Provincial People's Hospital, Zhengzhou, 450003 Henan, China.

出版信息

iScience. 2024 Dec 16;28(1):111614. doi: 10.1016/j.isci.2024.111614. eCollection 2025 Jan 17.

Abstract

Esophageal carcinoma (EC) is one of the most common malignant tumors in the world. ECRG4 has been recently discovered to be downregulated in EC. However, the mechanism leading to reduced expression of ECRG4 in esophageal cancer remains obscure. Here, we found that ECRG4 expression was significantly downregulated in EC tissues and cell lines. ECRG4 overexpression led to a significant decrease in proliferation and . Mechanistically, ECRG4 can activate IRF3/IFN-γ pathway. IFN-γ can promote the expression of miR-29b. MiR-29b reduces the expression of DNMT1. DNMT1 may affect the expression of ECRG4 by affecting the methylation of ECRG4 promoter. These results reveal ECRG4/IRF3/IFN-γ/miR-29b/DNMT1 positive feedback loop in esophageal carcinoma cells, which may become a potential therapeutic target for esophageal carcinoma.

摘要

食管癌(EC)是世界上最常见的恶性肿瘤之一。最近发现ECRG4在食管癌中表达下调。然而,食管癌中导致ECRG4表达降低的机制仍不清楚。在这里,我们发现ECRG4在食管癌组织和细胞系中表达明显下调。ECRG4过表达导致增殖显著降低。机制上,ECRG4可激活IRF3/IFN-γ通路。IFN-γ可促进miR-29b的表达。miR-29b可降低DNMT1的表达。DNMT1可能通过影响ECRG4启动子的甲基化来影响ECRG4的表达。这些结果揭示了食管癌细胞中ECRG4/IRF3/IFN-γ/miR-29b/DNMT1正反馈环,这可能成为食管癌的潜在治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef55/11742825/6ed1828fc231/fx1.jpg

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