Basic Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Oncol. Apr 24, 2024; 15(4): 554-565
Published online Apr 24, 2024. doi: 10.5306/wjco.v15.i4.554
Regulation of TMEM100 expression by epigenetic modification, effects on proliferation and invasion of esophageal squamous carcinoma
Yue-Feng Xu, Yan Dang, Wei-Bo Kong, Han-Lin Wang, Xiu Chen, Long Yao, Yuan Zhao, Ren-Quan Zhang
Yue-Feng Xu, Yan Dang, Wei-Bo Kong, Han-Lin Wang, Xiu Chen, Long Yao, Yuan Zhao, Ren-Quan Zhang, Department of Thoracic Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei 230000, Anhui Province, China
Author contributions: Xu YF and Dang Y are responsible for data curation and writing (original draft preparation); Kong WB is responsible for visualisation; Wang HL and Chen X are responsible for software and validation; Zhao Y is responsible for methodology; Yao L is responsible for writing (reviewing and editing); Zhang RQ is responsible for conceptualization and resources.
Institutional review board statement: This study does not involve human subjects.
Institutional animal care and use committee statement: This study does not involve animal subjects.
Conflict-of-interest statement: No conflicts of interest are associated with any of the senior authors or other co-authors who contributed their efforts to this manuscript.
Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author at a1285624638@163.com
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: Ren-Quan Zhang, MD, Surgeon, Department of Thoracic Surgery, The First Affiliated Hospital of Anhui Medical University, No. 218 Ji Xi Road, Hefei 230000, Anhui Province, China. zhangrenquanayfy@163.com
Received: January 2, 2024
Peer-review started: January 2, 2024
First decision: January 20, 2024
Revised: February 1, 2024
Accepted: March 20, 2024
Article in press: March 20, 2024
Published online: April 24, 2024
Processing time: 111 Days and 7.8 Hours
Abstract
BACKGROUND

Esophageal squamous cell carcinoma (ESCC) is a prevalent malignancy with a high morbidity and mortality rate. TMEM100 has been shown to be suppressor gene in a variety of tumors, but there are no reports on the role of TMEM100 in esophageal cancer (EC).

AIM

To investigate epigenetic regulation of TMEM100 expression in ESCC and the effect of TMEM100 on ESCC proliferation and invasion.

METHODS

Firstly, we found the expression of TMEM100 in EC through The Cancer Genome Atlas database. The correlation between TMEM100 gene expression and the survival of patients with EC was further confirmed through Kaplan-Meier analysis. We then added the demethylating agent 5-AZA to ESCC cell lines to explore the regulation of TMEM100 expression by epigenetic modification. To observe the effect of TMEM100 expression on tumor proliferation and invasion by overexpressing TMEM100. Finally, we performed gene set enrichment analysis using the Kyoto Encyclopaedia of Genes and Genomes Orthology-Based Annotation System database to look for pathways that might be affected by TMEM100 and verified the effect of TMEM100 expression on the mitogen-activated protein kinases (MAPK) pathway.

RESULTS

In the present study, by bioinformatic analysis we found that TMEM100 was lowly expressed in EC patients compared to normal subjects. Kaplan-meier survival analysis showed that low expression of TMEM100 was associated with poor prognosis in patients with EC. Then, we found that the demethylating agent 5-AZA resulted in increased expression of TMEM100 in ESCC cells [quantitative real-time PCR (qRT-PCR) and western blotting]. Subsequently, we confirmed that overexpression of TMEM100 leads to its increased expression in ESCC cells (qRT-PCR and western blotting). Overexpression of TMEM100 also inhibited proliferation, invasion and migration of ESCC cells (cell counting kit-8 and clone formation assays). Next, by enrichment analysis, we found that the gene set was significantly enriched in the MAPK signaling pathway. The involvement of TMEM100 in the regulation of MAPK signaling pathway in ESCC cell was subsequently verified by western blotting.

CONCLUSION

TMEM100 is a suppressor gene in ESCC, and its low expression may lead to aberrant activation of the MAPK pathway. Promoter methylation may play a key role in regulating TMEM100 expression.

Keywords: Esophageal squamous cell carcinoma; TMEM100; Invasion; Mitogen-activated protein kinases pathway; Epigenetic

Core Tip:TMEM100 has been shown to be an oncogene in a variety of tumors, but there are no reports on the role of TMEM100 in esophageal cancer. In the present study, we found that TMEM100 was lowly expressed in esophageal squamous cell carcinoma (ESCC). Methylation may play a key role in regulating TMEM100 protein low expression. Overexpression of TMEM100 resulted in its increased expression in ESCC cells. Overexpression of TMEM100 also inhibited proliferation, invasion and migration of ESCC cells. Low expression of TMEM100 in ESCC may lead to aberrant activation of the mitogen-activated protein kinases pathway.