ALKBH5-mediated CHAC1 depletion promotes malignant progression and decreases cisplatin-induced oxidative stress in gastric cancer

Chunting Chen; Ertao Zhai; Yinan Liu; Yan Qian; Risheng Zhao; Yan Ma; Jianqiu Liu; Zhixin Huang; Jianhui Chen; Shirong Cai

doi:10.1186/s12935-023-03129-9

ALKBH5-mediated CHAC1 depletion promotes malignant progression and decreases cisplatin-induced oxidative stress in gastric cancer

Cancer Cell Int. 2023 Nov 25;23(1):293. doi: 10.1186/s12935-023-03129-9.

Authors

Chunting Chen^#^{1

2

3}, Ertao Zhai^#^{1

2}, Yinan Liu^#^{1

2

3}, Yan Qian^{1

2}, Risheng Zhao^{1

2}, Yan Ma^{1

2}, Jianqiu Liu^{1

2}, Zhixin Huang^{1

2}, Jianhui Chen^{4

5}, Shirong Cai^{6

7}

Affiliations

¹ Division of Gastrointestinal Surgery Center, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, Guangdong, P. R. China.
² Gastric Cancer Center, Sun Yat-sen University, Guangzhou, 510080, Guangdong, P. R. China.
³ Laboratory of Surgery, The First Affiliated Hospital, Sun Yat-Sen University, No.58, Zhong Shan Er Lu, 510080, Guangzhou, P. R. China.
⁴ Division of Gastrointestinal Surgery Center, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, Guangdong, P. R. China. chenjh45@mail.sysu.edu.cn.
⁵ Gastric Cancer Center, Sun Yat-sen University, Guangzhou, 510080, Guangdong, P. R. China. chenjh45@mail.sysu.edu.cn.
⁶ Division of Gastrointestinal Surgery Center, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, Guangdong, P. R. China. caishr@mail.sysu.edu.cn.
⁷ Gastric Cancer Center, Sun Yat-sen University, Guangzhou, 510080, Guangdong, P. R. China. caishr@mail.sysu.edu.cn.

^# Contributed equally.

Abstract

The 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.

Keywords: ALKBH5; Gastric cancer; M6a; Oxidative stress.

Abstract

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