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©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
Checkpoint kinase 1 in colorectal cancer: Upregulation of expression and promotion of cell proliferation
Yu-Yan Pang, Zu-Yuan Chen, Da-Tong Zeng, Dong-Ming Li, Qi Li, Wan-Ying Huang, Bin Li, Jia-Yuan Luo, Bang-Teng Chi, Qiu Huang, Zhen-Bo Feng, Rong-Quan He
Yu-Yan Pang, Zu-Yuan Chen, Dong-Ming Li, Qi Li, Wan-Ying Huang, Bin Li, Jia-Yuan Luo, Bang-Teng Chi, Qiu Huang, Zhen-Bo Feng, Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
Da-Tong Zeng, Department of Pathology, Redcross Hospital of Yulin City, Yulin 537000, Guangxi Zhuang Autonomous Region, China
Rong-Quan He, Department of Medical Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
Co-first authors: Yu-Yan Pang and Zu-Yuan Chen.
Co-corresponding authors: Rong-Quan He and Zhen-Bo Feng.
Author contributions: Pang YY, Chen ZY, Zeng DT, Li DM, Li Q, Huang WY, Li B, Luo JY, Chi BT, Huang Q, Feng ZB, He RQ participated in the conception and designed the research study and performed the research; Pang YY and Chen ZY wrote the manuscript; Pang YY, Chen ZY and Zeng DT accessed and verified the study data. All authors critically reviewed and provided final approval of the manuscript; all authors were responsible for the decision to submit the manuscript for publication.
Supported by Innovation Project of Guangxi Graduate Education, No. YCBZ2023096; Guangxi Zhuang Autonomous Region Health Commission Scientific Research Project, No. Z20210442; China Undergraduate Innovation and Entrepreneurship Training Program, No. S202410598185; Future Academic Star of Guangxi Medical University, No. WLXSZX24101.
Institutional review board statement: This investigation was approved by the Institutional Ethics Committee of Yulin Red Cross Hospital.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
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: Zhen-Bo Feng, PhD, Doctor, Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Shuangyong Road, Nanning 530021, Guangxi Zhuang Autonomous Region, China.
fengzhenbo_gxmu@163.com
Received: September 25, 2024
Revised: November 4, 2024
Accepted: December 6, 2024
Published online: March 24, 2025
Processing time: 118 Days and 19.4 Hours
BACKGROUND
Colorectal cancer (CRC) is a prevalent malignant tumor characterized by a high mortality rate, with significant challenges persisting in the identification and management of its metastatic stage. The role of checkpoint kinase 1 (CHEK1), a cell cycle checkpoint kinase, in CRC has not been fully clarified. We hypothesize that the upregulation of CHEK1 may enhance the proliferation of CRC cells, indicating its potential as a novel therapeutic target for CRC therapy.
AIM
To investigate the expression and function of CHEK1 in CRC, this study utilizes single-cell RNA sequencing and tissue microarray data.
METHODS
Single-cell RNA sequencing technology was employed to analyze CRC cells from the GSE144735 dataset, and immunohistochemistry was conducted to confirm the expression of CHEK1 in CRC and adjacent tissues. We also integrated mRNA expression data from multiple public databases to assess global CHEK1 expression in CRC. Molecular docking experiments were performed to explore the interaction between CHEK1 and the potential drug nitidine chloride (NC), as well as to investigate the influence of CHEK1 on CRC cell proliferation.
RESULTS
We found comparatively elevated CHEK1 expression in the malignant epithelial cells of CRC, with marked upregulation of its mRNA levels in CRC tissues. Immunohistochemical analysis further confirmed the high expression of CHEK1 in CRC tissues, and the receiver operating characteristic curve demonstrated high accuracy (area under the curve = 0.964) for CHEK1 as a biomarker. Analysis of global datasets indicated a statistically significant overexpression of CHEK1 in CRC (standard mean difference = 1.81, P < 0.01), with summary receiver operating characteristic analysis yielding sensitivity and specificity values of 0.83 and 0.88, respectively. Molecular docking studies indicated that NC specifically targeted CHEK1, while clustered regularly interspaced short palindromic repeats knockout experiments demonstrated that CHEK1 promoted CRC cell proliferation.
CONCLUSION
Upregulation of CHEK1 promotes CRC cell proliferation. However, the dataset's diversity is limited, requiring further investigation into its specific mechanisms.
Core Tip: This study demonstrates that checkpoint kinase 1 (CHEK1) is comparatively overexpressed in colorectal cancer (CRC) and is closely associated with tumor proliferation. Based on single-cell RNA sequencing and immunohistochemistry, the findings highlight CHEK1’s potential as a novel biomarker and therapeutic target in CRC. Furthermore, the research uncovers nitidine chloride as a specific CHEK1 inhibitor, suggesting promising avenues for targeted therapies to improve patient outcomes. These insights underscore the clinical relevance of CHEK1 in CRC management and the need for further exploration of its mechanistic roles.
