METTL14 Inhibits Malignant Progression of Oral Squamous Cell Carcinoma by Targeting the Autophagy-related Gene RB1CC1 in an M6A-IGF2BP2-dependent Manner

Overview

Journal Clin Sci (Lond)

Specialties Biochemistry
General Medicine
Science

Date 2023 Aug 24

PMID 37615536

Authors

Jianfeng Liang

Hongshi Cai

Chen Hou

Fan Song

Yaoqi Jiang

Ziyi Wang

Danqi Qiu

Yue Zhu

Fang Wang

Dongsheng Yu

Jinsong Hou

Affiliations

Soon will be listed here.

Abstract

N6-methyladenosine (m6A) plays crucial roles in tumorigenesis and autophagy. However, the underlying mechanisms mediated by m6A and autophagy in the malignant progression of oral squamous cell carcinoma (OSCC) remain unclear. In the present study, we revealed that down-regulated expression of METTL14 was correlated with advanced clinicopathological characteristics and poor prognosis in OSCC. METTL14 knockdown significantly inhibited autophagy and facilitated malignant progression in vitro, and promoted tumor growth and metastasis in vivo. A cell model of rapamycin-induced autophagy was established to identify RB1CC1 as a potential target gene involved in m6A-regulated autophagy in OSCC, through RNA sequencing and methylated RNA immunoprecipitation sequencing (meRIP-seq) analysis. Mechanistically, we confirmed that METTL14 posttranscriptionally enhanced RB1CC1 expression in an m6A-IGF2BP2-dependent manner, thereby affecting autophagy and progression in OSCC, through methylated RNA immunoprecipitation qRT-PCR (meRIP-qPCR), RNA stability assays, mutagenesis assays and dual-luciferase reporter. Collectively, our findings demonstrated that METTL14 serves as an OSCC suppressor by regulating the autophagy-related gene RB1CC1 through m6A modification, which may provide a new insight for the diagnosis and therapy of OSCC.

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