The METTL3-m6A-YTHDC1-AMIGO2 axis contributes to cell proliferation and migration in esophageal squamous cell carcinoma
[Display omitted] •Silencing METTL3 led to a decreased m6A modification in the 5′UTR of AMIGO2 pre-mRNA.•YTHDC1 interacted with m6A-modified pre-mRNA of AMIGO2 to regulate its splicing.•AMIGO2 was a downstream target of both METTL3 and YTHDC1.•AMIGO2 contributed to the malignant behaviors of ESCC ce...
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Published in | Gene Vol. 908; p. 148281 |
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Main Authors | , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Elsevier B.V
25.05.2024
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Subjects | |
Online Access | Get full text |
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Summary: | [Display omitted]
•Silencing METTL3 led to a decreased m6A modification in the 5′UTR of AMIGO2 pre-mRNA.•YTHDC1 interacted with m6A-modified pre-mRNA of AMIGO2 to regulate its splicing.•AMIGO2 was a downstream target of both METTL3 and YTHDC1.•AMIGO2 contributed to the malignant behaviors of ESCC cells in vitro and in vivo.•The METTL3-m6A-YTHDC1-AMIGO2 axis might play critical role in ESCC.
The upregulation of methyltransferase-like 3 (METTL3) has been associated with the progression of esophageal cancer. However, METTL3-induced N6-methyladenosine (m6A) 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 m6A 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-m6A-YTHDC1-AMIGO2 axis in regulating ESCC cell proliferation and motility, suggesting its potential as a therapeutic target for ESCC. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0378-1119 1879-0038 |
DOI: | 10.1016/j.gene.2024.148281 |