Copyright
©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
Correlations of the expression of Cx43, SCFFBXW7, p-cyclin E1 (Ser73), p-cyclin E1 (Thr77) and p-cyclin E1 (Thr395) in colon cancer tissues
Rong-Gang Luan, Ming-Da Liu, Zi-Feng Deng, Cong-Lan Lu, Mei-Ling Yu, Ming-Yu Zhang, Rong Liu, Ran An, You-Liang Yao, Dong-Bei Guo, Yong-Xing Zhang, Lei Zhao
Rong-Gang Luan, Department of Gastrointestinal Surgery, Air Force Hospital of Eastern Theater, Anhui Medical University, Nanjing 230032, Jiangsu Province, China
Ming-Da Liu, Zi-Feng Deng, Rong Liu, Ran An, You-Liang Yao, Dong-Bei Guo, Yong-Xing Zhang, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen 361102, Fujian Province, China
Cong-Lan Lu, Mei-Ling Yu, Ming-Yu Zhang, Trauma Surgery, Air Force Hospital of Eastern Theater, Anhui Medical University, Nanjing 230032, Jiangsu Province, China
Lei Zhao, Department of Orthopaedics, Air Force Hospital of Eastern Theater, Anhui Medical University, Nanjing 230032, Jiangsu Province, China
Co-corresponding authors: Yong-Xing Zhang and Lei Zhao.
Author contributions: Zhang YX and Zhao L designed the research study; Luan RG, Liu MD and Deng ZF performed the research; Lu CL, Zhang MY, Liu R and Yu ML analyzed the data; Zhao L contributed of pathological tissues; Luan RG wrote the manuscript; An R, Yao YL and Guo DB gave administrative support. All authors have read and approved the final manuscript. Professor Zhang YX and Zhao L jointly designed the experiment. Professor Zhang YX provided most of the experimental platforms and techniques, while Zhao L provided pathological tissues and annotated corresponding general conditions and clinical stages. Subsequent to the initial drafting phase, Professor Zhang YX and Zhao L have contributed equally to the iterative revisions of the manuscript. Following a comprehensive deliberation involving all co-authors, it has been mutually agreed that Professor Zhang YX and Dr. Zhao L be designated as co-corresponding authors.
Supported by Innovative Practice Platform for Undergraduate Students, School of Public Health Xiamen University, No. 2021001.
Institutional review board statement: The experimental design and protocol of this study fully consider the principles of safety and fairness, and its research content will not cause harm or risk to the research subjects. The research subject belongs to the principle of voluntariness, the right to know is guaranteed, and the rights and privacy of the research subject will be maximally protected.
Conflict-of-interest statement: The authors have no conflicts of interest to declare.
Data sharing statement: All original slices are kept by our laboratory. Please contact
z63y94x@xmu.edu.cn for relevant data.
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: Lei Zhao, MD, PhD, Attending Doctor, Surgeon, Department of Orthopaedics, Air Force Hospital of Eastern Theater, Anhui Medical University, No. 1 Changfu Road, Malu Road, Nanjing 230032, Jiangsu Province, China.
18742583975@163.com
Received: June 25, 2024
Revised: October 13, 2024
Accepted: October 28, 2024
Published online: January 15, 2025
Processing time: 169 Days and 18.1 Hours
BACKGROUND
Previous cellular studies have demonstrated that elevated expression of Cx43 promotes the degradation of cyclin E1 and inhibits cell proliferation through ubiquitination. Conversely, reduced expression results in a loss of this capacity to facilitate cyclin E degradation. The ubiquitination and degradation of cyclin E1 may be associated with phosphorylation at specific sites on the protein, with Cx43 potentially enhancing this process by facilitating the phosphorylation of these critical residues.
AIM
To investigate the correlation between expression of Cx43, SKP1/Cullin1/F-box (SCF)FBXW7, p-cyclin E1 (ser73, thr77, thr395) and clinicopathological indexes in colon cancer.
METHODS
Expression levels of Cx43, SCFFBXW7, p-cyclin E1 (ser73, thr77, thr395) in 38 clinical colon cancer samples were detected by immunohistochemistry and were analyzed by statistical methods to discuss their correlations.
RESULTS
Positive rate of Cx43, SCFFBXW7, p-cyclin E1(Ser73), p-cyclin E1 (Thr77) and p-cyclin E1 (Thr395) in detected samples were 76.32%, 76.32%, 65.79%, 5.26% and 55.26% respectively. Positive expressions of these proteins were not related to the tissue type, degree of tissue differentiation or lymph node metastasis. Cx43 and SCFFBXW7(r = 0.749), p-cyclin E1 (Ser73) (r = 0.667) and p-cyclin E1 (Thr395) (r = 0.457), SCFFBXW7 and p-cyclin E1 (Ser73) (r = 0.703) and p-cyclin E1 (Thr395) (0.415) were correlated in colon cancer (P < 0.05), and expressions of the above proteins were positively correlated in colon cancer.
CONCLUSION
Cx43 may facilitate the phosphorylation of cyclin E1 at the Ser73 and Thr195 sites through its interaction with SCFFBXW7, thereby influencing the ubiquitination and degradation of cyclin E1.
Core Tip: In this study, we found that SKP1/Cullin1/F-box (SCF)FBXW7 exhibited a positive correlation with cyclin E1 expression at positions ser73 and thr395 in colon cancer tissues, suggesting that SCFFBXW7 may facilitate phosphorylation-dependent degradation by interacting with cyclin E1 at these specific sites. Furthermore, the expressions of Cx43 and SCFFBXW7 were positively correlated, as well as their association with the levels at positions ser73 and thr395. This indicates that Cx43 may enhance the phosphorylation of these two sites through its interaction with SCFFBXW7, thereby promoting the ubiquitination and degradation of cyclin E1.
