Zhang YQ, Li J, Qin Z, Li DM, Ye FZ, Bei SH, Zhang XH, Feng L. METTL5 promotes gastric cancer progression via sphingomyelin metabolism. World J Gastrointest Oncol 2024; 16(5): 1925-1946 [PMID: 38764837 DOI: 10.4251/wjgo.v16.i5.1925]
Corresponding Author of This Article
Li Feng, PhD, Chief Physician, Endoscopy Center, Minhang Hospital Affiliated to Fudan University, No. 138 Medical College Road, Xuhui District, Shanghai 201100, China. feng_li@fudan.edu.cn
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Clinical and Translational Research
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Gastrointest Oncol. May 15, 2024; 16(5): 1925-1946 Published online May 15, 2024. doi: 10.4251/wjgo.v16.i5.1925
METTL5 promotes gastric cancer progression via sphingomyelin metabolism
Ya-Qiong Zhang, Jian Li, Zhe Qin, De-Ming Li, Fang-Zhou Ye, Song-Hua Bei, Xiao-Hong Zhang, Li Feng
Ya-Qiong Zhang, Jian Li, Zhe Qin, De-Ming Li, Fang-Zhou Ye, Song-Hua Bei, Xiao-Hong Zhang, Li Feng, Endoscopy Center, Minhang Hospital Affiliated to Fudan University, Shanghai 201100, China
Co-corresponding authors: Xiao-Hong Zhang and Li Feng.
Author contributions: Zhang YQ and Feng L designed the framework of the entire article; Zhang XH and Feng L provided funding support; Zhang YQ completed the entire manuscript; and Qin Z, Li DM, Ye FZ, Bei SH completed the experimental part of the article. All authors were involved in the critical review of the results and have contributed to, read, and approved the final manuscript. Zhang XH and Feng L contributed equally to this work as co-corresponding authors. The reasons for designating Zhang XH and Feng L as co-corresponding authors are as followed. Firstly, the research funding was jointly provided by Zhang XH and Feng L; Secondly, Feng L provided extensive guidance on the epidemiology and clinical treatment status of gastric cancer at the beginning of the project design; Zhang XH provided extensive guidance in analyzing experimental data and answering questions. So, Zhang XH and Feng L can serve as co-corresponding authors of this manuscript.
Institutional review board statement: This study was reviewed and approved by the Ethics Committee of Minhang Hospital Affiliated to Fudan University.
Informed consent statement: All study participants or their legal guardian provided informed written consent about personal and medical data collection prior to study enrolment.
Conflict-of-interest statement: This manuscript has not been published or presented elsewhere in part or in entirety and is not under consideration by another journal. There are no conflicts of interest to declare.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Li Feng, PhD, Chief Physician, Endoscopy Center, Minhang Hospital Affiliated to Fudan University, No. 138 Medical College Road, Xuhui District, Shanghai 201100, China. feng_li@fudan.edu.cn
Received: December 11, 2023 Peer-review started: December 11, 2023 First decision: December 29, 2023 Revised: January 9, 2024 Accepted: February 19, 2024 Article in press: February 19, 2024 Published online: May 15, 2024
ARTICLE HIGHLIGHTS
Research background
Previous study reported that METTL5 plays a pivotal role in maintaining the metabolic stability of cells. However, its aberrant regulation in gastric cancer (GC) has not been fully elucidated.
Research motivation
To find new targets for the therapy of GC.
Research objectives
To excavate the role and potential mechanism of METTL5 in the development of GC.
Research methods
The Cancer Genome Atlas (TCGA) dataset, immunohistochemistry (IHC), western blotting and real-time quantitative polymerase chain reaction were used to analyze the expression of METTL5. The Cell Counting Kit-8 assays, colony formation assays, scratch healing assays, Transwell assays and flow cytometry and xenograft tumor model were used to explore effect of METTL5 on GC. Next, liquid chromatography-mass spectrometry (LC-MS) was used to evaluate the association between METTL5 and sphingomyelin metabolism.
Research results
An upregulation of METTL5 suggested a poor prognosis of GC patients. Increased METTL5 expression implied distant lymph node metastasis, advanced cancer stage, pathological grade and a high degree of m6A methylation. METTL5 promotes the proliferation, migration, and invasion of GC cells in vitro. METTL5 knockdown resulted in significant changes in sphingomyelin metabolism. In addition, high METTL5 expression led to cisplatin resistance.
Research conclusions
The upregulation of METTL5 suggested a poor prognosis of GC patients. METTL5 markedly promotes the proliferation, migration, and invasion of GC cells in vitro. METTL5 also promotes the growth of GC in animal models. METTL5 knockdown resulted in significant changes in sphingomyelin metabolism. In addition, high METTL5 expression led to cisplatin resistance.
Research perspectives
The mechanism between METTL5 and sphingomyelin metabolism in GC is worth further research.
