The METTL3-m 6 A-YTHDC1-AMIGO2 axis contributes to cell proliferation and migration in esophageal squamous cell carcinoma.

Autor: Qiu Y; Department of Cell Biology, Yangzhou University Medical College, Yangzhou, Jiangsu, China., Tian Z; Department of Cell Biology, Yangzhou University Medical College, Yangzhou, Jiangsu, China., Miao TY; Department of Cell Biology, Yangzhou University Medical College, Yangzhou, Jiangsu, China., Shen L; Department of Cell Biology, Yangzhou University Medical College, Yangzhou, Jiangsu, China., Chen J; Department of Cell Biology, Yangzhou University Medical College, Yangzhou, Jiangsu, China., Li PF; Department of Cell Biology, Yangzhou University Medical College, Yangzhou, Jiangsu, China., Zhu ZX; Department of Cell Biology, Yangzhou University Medical College, Yangzhou, Jiangsu, China., Zhu ZF; Department of Cell Biology, Yangzhou University Medical College, Yangzhou, Jiangsu, China., Wu WJ; Department of Oncology, Clinical Medical College, Yangzhou University, Yangzhou, Jiangsu, China., Xu X; Department of Oncology, Taizhou Hospital of Traditional Chinese Medicine, Taizhou, Jiangsu, China. Electronic address: dr_xuxiao@yeah.net., Shen WG; Department of Cell Biology, Yangzhou University Medical College, Yangzhou, Jiangsu, China; Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Yangzhou University, Yangzhou, Jiangsu, China. Electronic address: shenwg@yzu.edu.cn.
Jazyk: angličtina
Zdroj: Gene [Gene] 2024 May 25; Vol. 908, pp. 148281. Date of Electronic Publication: 2024 Feb 13.
DOI: 10.1016/j.gene.2024.148281
Abstrakt: The upregulation of methyltransferase-like 3 (METTL3) has been associated with the progression of esophageal cancer. However, METTL3-induced N 6 -methyladenosine (m 6 A) alterations on the downstream target mRNAs in esophageal squamous cell carcinoma (ESCC) are not yet fully understood. Our study revealed that silencing METTL3 resulted in a significant decrease in ESCC cell proliferation and metastasis in vitro and in vivo. Additionally, the adhesion molecule with Ig like domain 2 (AMIGO2) was identified as a potential downstream target of both METTL3 and YTH Domain-Containing Protein 1 (YTHDC1) in ESCC cells. Functionally, AMIGO2 augmented the malignant behaviors of ESCC cells in vitro and in vivo, and its overexpression can rescue the inhibition of the proliferation and migration in ESCC cells induced by METTL3 or YTHDC1 knockdown. Furthermore, our findings revealed that knockdown of METTL3 decreased m 6 A modification in the 5'-untranslated regions (5'UTR) of AMIGO2 precursor mRNA (pre-mRNA), and YTHDC1 interacted with AMIGO2 pre-mRNA to regulate AMIGO2 expression by modulating the splicing process of AMIGO2 pre-mRNA in ESCC cells. These findings highlighted a novel role of the METTL3-m 6 A-YTHDC1-AMIGO2 axis in regulating ESCC cell proliferation and motility, suggesting its potential as a therapeutic target for ESCC.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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