Author:
Chen Chunting,Zhai Ertao,Liu Yinan,Qian Yan,Zhao Risheng,Ma Yan,Liu Jianqiu,Huang Zhixin,Chen Jianhui,Cai Shirong
Abstract
AbstractThe m6a demethyltransferase ALKBH5 dynamically modulates gene expression and intracellular metabolic molecules by modifying RNA m6a in cancer cells. However, ALKBH5’s function in gastric cancer (GC) has remained controversial. This study demonstrates that ALKBH5 is highly expressed in GC. Silencing ALKBH5 hampers proliferation, and metastatic potential, and induces cell death in GC cells. Through a comprehensive analysis of the transcriptome and m6A sequencing, alterations in certain ALKBH5 target genes, including CHAC1, were identified. ALKBH5’s demethylation effect regulates CHAC1 RNA stability, leading to reduced CHAC1 expression. Moreover, CHAC1 modulates intracellular ROS levels, influencing the chemotherapy sensitivity of gastric cancer. In summary, our study unveils the pivotal role of the ALKBH5-CHAC1-ROS axis and highlights the significance of m6A methylation in gastric cancer.
Funder
National Natural Science Foundation of China
Young Teacher Training Project of The First Affiliated Hospital of Sun Yat-sen University
Basic and Applied Basic Research Foundation of Guangdong Province
Guangzhou Basic and Applied Basic Research Foundation
Project 5010 of The First Affiliated Hospital of Sun Yat-sen University
Publisher
Springer Science and Business Media LLC
Subject
Cancer Research,Genetics,Oncology
Cited by
1 articles.
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