Journal Article

FOXD2-AS1 is modulated by METTL3 with the assistance of YTHDF1 to affect proliferation and apoptosis in esophageal cancer

Liu, Xing Chen, Wang, Zijin, Gao, Zhen Gya, Wang, Wen Cai, Shi, Wo Da

2025

Overview

This study aims to investigate the regulatory mechanisms of METTL3, YTHDF1, and the long non-coding RNA FOXD2-AS1 in the proliferation and apoptosis of esophageal cancer, with the goal of providing a basis for molecular diagnosis and targeted therapies. Gene expression was evaluated using qRT-PCR (METTL3/14) and Western blot analysis. The Cell Counting Kit-8 (CCK-8) assay, flow cytometry, and Transwell assay were employed to assess cell proliferation and apoptosis. The EpiQuik m6A RNA Methylation Quantification Kit was utilized to quantify total m6A levels. The interaction between YTHDF1, FOXD2-AS1, and METTL3 was confirmed using RNA Binding Protein Immunoprecipitation (RIP), Co-Immunoprecipitation (CO-IP), and RNA pull-down assays. Methylated RNA Immuno preci pitation (MeRIP) was employed to assess the m6A modification levels of FOXD2-AS1. Tissue samples from animal models were analyzed via Hematoxylin-eosin staining (HE) staining and immunohisto-chemistry to assess METTL3 expression. The expression of was up-regulated in esophageal cancer tissues and cells. Flow cytometry and CCK-8 detection showed that silencing could inhibit the proliferation of esophageal cancer cells but accelerate their apoptosis. MeRIP-qPCR and Prediction of m6A-modified sites indicated that METTL3 regulated the m6A modification of FOXD2-AS1. and experiments showed that YTHDF1 binds to METTL3 and regulates the m6A modification of FOXD2-AS1 to affect esophageal cancer. Our results indicate that METTL3 regulates FOXD2-AS1 in an m6A-dependent manner through its interaction with YTHDF1, thereby influencing EC proliferation and apoptosis. This suggests a potential therapeutic target for the treatment of esophageal cancer.

• Publisher: Sciendo,De Gruyter Brill Sp. z o.o., Paradigm Publishing Services,Hrvatsko farmaceutsko društvo
• Subject: Animal models / Animals / Apoptosis / Apoptosis - genetics / Cancer / Cell Line, Tumor / Cell proliferation / Cell Proliferation - genetics / Cholecystokinin / Esophageal cancer / Esophageal Neoplasms - genetics / Esophageal Neoplasms - metabolism / Esophageal Neoplasms - pathology / Esophagus / Female / Flow cytometry / FOXD2-AS1 / Gene expression / Gene Expression Regulation, Neoplastic / Humans / Immunoprecipitation / Male / Methyltransferases - genetics / Methyltransferases - metabolism / METTL3 / Mice / Mice, Inbred BALB C / Mice, Nude / N6-methyladenosine / RNA, Long Noncoding - genetics / RNA, Long Noncoding - metabolism / RNA-binding protein / RNA-Binding Proteins - genetics / RNA-Binding Proteins - metabolism / Therapeutic targets / YTHDF1