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©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
METTL5 promotes cell proliferation, invasion, and migration by up-regulating Toll-like receptor 8 expression in colorectal cancer
Ling-Shang Kong, Ran Tao, Yi-Fan Li, Wen-Bin Wang, Xue Zhao
Ling-Shang Kong, Ran Tao, Yi-Fan Li, Wen-Bin Wang, Department of General Surgery, The Second Affiliated Hospital of Anhui Medical University, Hefei 230001, Anhui Province, China
Ling-Shang Kong, Ran Tao, Yi-Fan Li, Wen-Bin Wang, Department of Vascular Surgery, The Second Affiliated Hospital of Anhui Medical University, Hefei 230002, Anhui Province, China
Wen-Bin Wang, Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei 230001, Anhui Province, China
Wen-Bin Wang, Anhui Public Health Clinical Center, Hefei 230012, Anhui Province, China
Xue Zhao, Department of Scientific Research, Anhui Public Health Clinical Center, Hefei 230012, Anhui Province, China
Xue Zhao, Department of Scientific Research, The First Affiliated Hospital of Anhui Medical University, Hefei 230001, Anhui Province, China
Co-corresponding authors: Wen-Bin Wang and Xue Zhao.
Author contributions: Kong LS, Tao R, and Li YF collected the data, performed the experiments and statistical analysis, and wrote the manuscript; Wang WB and Zhao X designed the study and performed quality control. Kong LS and Tao R contributed equally to this work. Wang WB and Zhao X made outstanding contributions to this study as co-corresponding authors.
Supported by Natural Science Foundation in Anhui Province of China, No. 2008085MH279; and Key Project of Anhui Translational Medicine Research Institute, No. 2022zhyx-B08.
Institutional review board statement: The study was reviewed and approved by the First Affiliated Hospital of Anhui Medical University Institutional Review Board (approval No. 190278).
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: Data are available upon reasonable request.
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: Xue Zhao, MM, Department of Scientific Research, Anhui Public Health Clinical Center, No. 100 Huaihai Avenue, Hefei 230012, Anhui Province, China. 472959583@qq.com
Received: September 13, 2023
Peer-review started: September 13, 2023
First decision: December 14, 2023
Revised: January 10, 2024
Accepted: March 18, 2024
Article in press: March 18, 2024
Published online: May 15, 2024
BACKGROUND
N6-methyladenosine (m6A) modification represents the predominant alteration found in eukaryotic messenger RNA and plays a crucial role in the progression of various tumors. However, despite its significance, the comprehensive investigation of METTL5, a key m6A methyltransferase, in colorectal cancer (CRC) remains limited.
AIM
To investigate the role of METTL5 in CRC.
METHODS
We assessed METTL5 expression levels in clinical samples obtained from CRC patients as well as in CRC cell lines. To elucidate the downstream targets of METTL5, we performed RNA-sequencing analysis coupled with correlation analysis, leading us to identify Toll-like receptor 8 (TLR8) as a potential downstream target. In vitro functional assessments of METTL5 and TLR8 were conducted using CCK-8 assays, scratch assays, as well as assays measuring cell migration and invasion.
RESULTS
Our findings reveal a pronounced upregulation of METTL5 expression in both CRC cells and tissues, which correlated significantly with an unfavorable prognosis. In vitro experiments unequivocally demonstrated the oncogenic role of METTL5, as evidenced by its promotion of CRC cell proliferation, invasion, and migration. Notably, we identified TLR8 as a downstream target of METTL5, and subsequent down-regulation of TLR8 led to a significant inhibition of CRC cell proliferation, invasion, and tumor growth.
CONCLUSION
The heightened expression of METTL5 in CRC is strongly associated with clinicopathological features and a poor prognosis, thereby underscoring its potential utility as a critical marker for facilitating early diagnosis and prognostication in CRC.
Core Tip: N6-methyladenosine is one of the most common post-transcriptional RNA modifications in mammals and one of the major methylation modifications in mRNA and non-coding RNAs, which can affect RNA splicing, translation, stability, and epigenetic effects of certain non-coding RNAs. This is the first fundamental study to examine the role of METTL5 in colorectal cancer (CRC), which is important for understanding the impact of the METTL family on the development of CRC.
