m6A Methyltransferase METTL3 Reduces Hippocampal Neuron Apoptosis in a Mouse Model

• 발행기관: 대한신경정신의학회
• 저자명: Yue Ming Zhihui Deng Xianhua Tian Yuerong Jia Meng Ning Shuhua Cheng
• 간행물 정보: 『Psychiatry Investigation』제19권 제10호, 771~789쪽, 전체 19쪽
• 주제분류: 의약학 > 정신과학
• 파일형태: PDF
• 발행일자: 2022.10.31

영문 초록

Objective Hippocampal neuron apoptosis contributes to autism, while METTL3 has been documented to possess great potentials in neuron apoptosis. Our study probed into the role of METTL3 in neuron apoptosis in autism and to determine the underlying mechanism. Methods Bioinformatics analysis was used to analyze expressed genes in autism samples. Institute of Cancer Research mice were treated with valproic acid to develop autism models. The function of METTL3 in autism-like symptoms in mice was analyzed with behavioral tests and histological examination of their hippocampal tissues. Primary mouse hippocampal neurons were extracted for in vitro studies. Downstream factors of METTL3 were explored and validated. Results METTL3, MALAT1, and Wnt/β-catenin signaling were downregulated, while SFRP2 was upregulated in the hippocampal tissues of a mouse model of autism. METTL3 stabilized MALAT1 expression by promoting m6A modification of MALAT1. MALAT1 promoted SFRP2 methylation and led to reduced SFRP2 expression by recruiting DNMT1, DNMT3A, and DNMT3B to the promoter region of SFRP2. Furthermore, SFRP2 facilitated activation of the Wnt/β-catenin signaling. By this mechanism, METTL3 suppressed autism-like symptoms and hippocampal neuron apoptosis. Conclusion This research suggests that METTL3 can reduce autism-like symptoms and hippocampal neuron apoptosis by regulating the MALAT1/SFRP2/Wnt/β-catenin axis.

목차

INTRODUCTION

METHODS

RESULTS

DISCUSSION

키워드

Autism Methyltransferase like-3 Long noncoding RNA MALAT1 DNA methyltransferase Secreted Frizzled Related Protein 2 Wnt/β-catenin signaling Hippocampal neurons