METTL3/IGF2BP2 Promotes the Malignant Progression of Esophageal Cancer by Activating the PIK3CA/AKT Pathway

Overview

Journal Thorac Cancer

Specialties Oncology
Pulmonary Medicine

Date 2025 Feb 21

PMID 39980152

Authors

Xinmeng Guo

Anqi Huang

Yanan Qi

Jiaqi Chen

Meng Yang

Mulan Jin

Affiliations

Soon will be listed here.

Abstract

Esophageal cancer (EC) is a leading cause of cancer-related mortality worldwide. Methyltransferase-like 3 (METTL3), a key enzyme involved in m6A methylation, has been implicated in the development and progression of various cancers, including EC. However, its potential mechanism of action in EC progression remains unclear. METTL3 expression was found to be upregulated in EC tissues and cells. Knockdown of METTL3 suppressed EC cell proliferation, invasion, migration, and angiogenesis, while promoting apoptosis. Mechanistically, METTL3 maintained PIK3CA mRNA expression and stability in an m6A-dependent and IGF2BP2-dependent manner, respectively. METTL3 silencing inactivated the AKT pathway by regulating PIK3CA expression. Furthermore, overexpression of PIK3CA mitigated the effects of METTL3 silencing on the malignant growth of KYSE180 and TE1 cells in vivo and in vitro. METTL3/IGF2BP2 promoted the malignant progression of EC by activating the PIK3CA/AKT pathway. Targeting the METTL3-PIK3CA axis may offer a novel therapeutic approach for EC treatment.

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