Xin MJ, Yuan Y. Centromere protein A knockdown inhibits rectal cancer through O6-methylguanine DNA methyltransferase/protein tyrosine phosphatase nonreceptor type 4 axis. World J Gastrointest Oncol 2025; 17(4): 102619 [DOI: 10.4251/wjgo.v17.i4.102619]
Corresponding Author of This Article
Ming-Jie Xin, BM, Medical College, Henan Vocational University of Science and Technology, No. 6 East Section of Wenchang Avenue, Zhoukou 466000, Henan Province, China. xinmingjie_1985@126.com
Research Domain of This Article
Oncology
Article-Type of This Article
Basic Study
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. Apr 15, 2025; 17(4): 102619 Published online Apr 15, 2025. doi: 10.4251/wjgo.v17.i4.102619
Centromere protein A knockdown inhibits rectal cancer through O6-methylguanine DNA methyltransferase/protein tyrosine phosphatase nonreceptor type 4 axis
Ming-Jie Xin, Yong Yuan
Ming-Jie Xin, Yong Yuan, Medical College, Henan Vocational University of Science and Technology, Zhoukou 466000, Henan Province, China
Author contributions: Xin MJ designed the research study and performed the research; Yuan Y analyzed the data and wrote the manuscript; All authors have read and approved the final manuscript.
Institutional review board statement: This study was reviewed and approved by the Ethic Committee of Medical College of Henan Vocational University of Science and Technology (Approval No. HVUYL414101416920231017001), and all participants signed a written informed consent.
Institutional animal care and use committee statement: All animal experiments were approved by the Animal Ethics Committee of the Medical College of Henan Vocational University of Science and Technology (Approval No. HVUYL414101416920240603001).
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
ARRIVE guidelines statement: The authors have read the ARRIVE Guidelines, and the manuscript was prepared and revised according to the ARRIVE Guidelines.
Data sharing statement: The datasets used during the present study are available from the corresponding author upon reasonable request (E-mail: xinmingjie_1985@126.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: Ming-Jie Xin, BM, Medical College, Henan Vocational University of Science and Technology, No. 6 East Section of Wenchang Avenue, Zhoukou 466000, Henan Province, China. xinmingjie_1985@126.com
Received: October 24, 2024 Revised: January 7, 2025 Accepted: February 25, 2025 Published online: April 15, 2025 Processing time: 153 Days and 7.8 Hours
Abstract
BACKGROUND
Centromere protein A (CENPA) exhibits an increased expression level in primary human rectal cancer tissues, but its role has not been investigated.
AIM
To clarify the specific role and mechanism of CENPA in rectal cancer progression.
METHODS
CENPA protein expression in rectal cancer tissues and cell lines were detected. CENPA was overexpressed and knocked down in SW837 and SW480 cells, and proliferation, invasion, apoptosis and epithelial-mesenchymal transition (EMT) marker protein levels were examined. O6-methylguanine DNA methyltransferase (MGMT) promoter methylation was assessed with methylation-specific polymerase chain reaction. Co-immunoprecipitation assay verified the interaction between MGMT and protein tyrosine phosphatase nonreceptor type 4 (PTPN4). SW837 cells with CENPA knockdown were injected subcutaneously into mice, and tumor growth was examined.
RESULTS
CENPA was upregulated in rectal cancer tissues and cell lines. CENPA overexpression promoted proliferation, invasion and EMT, and inhibited apoptosis in rectal cancer cells. Whereas CENPA knockdown showed the opposite results. Moreover, CENPA inhibited MGMT expression by promoting DNA methyltransferase 1-mediated MGMT promoter methylation. MGMT knockdown abolished the CENPA knockdown-mediated inhibition of rectal cancer cell progression. MGMT increased PTPN4 protein stability by inhibiting PTPN4 ubiquitination degradation via competing with ubiquitin-conjugating enzyme E2O for interacting with PTPN4. PTPN4 knockdown abolished the inhibitory effects of MGMT overexpression on rectal cancer cell progression. Moreover, CENPA knockdown inhibited xenograft tumor growth in vivo.
CONCLUSION
CENPA knockdown inhibited rectal cancer cell growth and attenuated xenograft tumor growth through regulating the MGMT/PTPN4 axis.
Core Tip: This study suggested that centromere protein A (CENPA) was upregulated in rectal cancer tissues and cell lines. CENPA overexpression promoted proliferation, invasion and epithelial-mesenchymal transition, and inhibited apoptosis in rectal cancer cells. Whereas CENPA knockdown showed the opposite results. Additionally, CENPA knockdown inhibited xenograft tumor growth in vivo. Mechanistically, CENPA inhibited O6-methylguanine DNA methyltransferase (MGMT) expression by promoting DNA methyltransferase 1-mediated MGMT promoter methylation. MGMT interacted with protein tyrosine phosphatase nonreceptor type 4 (PTPN4) and increased PTPN4 protein stability. CENPA knockdown inhibited rectal cancer progression through regulating the MGMT/PTPN4 axis.
