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©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
Nitidine chloride may mediate its antitumor effects by targeting kinesin family member 20A in colorectal cancer cells
Ke-Jun Wu, Da-Tong Zeng, Rong-Quan He, Dong-Ming Li, Jin-Lian Yao, Li-Min Liu, Wei-Jian Huang, Di-Yuan Qin, Yu-Feng Li, Han He, Shi-De Li, Jia-Ying Wen, Li Meng, Jia-Rong Shi, Gang Chen, Hui Li
Ke-Jun Wu, Da-Tong Zeng, Dong-Ming Li, Yu-Feng Li, Han He, Shi-De Li, Gang Chen, Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Guangxi Medical University, Nanning 530021, 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
Jin-Lian Yao, Department of Pharmacy, Guangxi Medical University Cancer Hospital, Nanning 530021, Guangxi Zhuang Autonomous Region, China
Li-Min Liu, Department of Toxicology, College of Pharmacy, Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
Wei-Jian Huang, Department of Pathology, Redcross Hospital of Yulin City, Yulin 537000, Guangxi Zhuang Autonomous Region, China
Di-Yuan Qin, Department of Computer Science and Technology, School of Computer and Electronic Information, Guangxi University, Nanning 530004, Guangxi Zhuang Autonomous Region, China
Jia-Ying Wen, Department of Radiotherapy, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
Li Meng, Jia-Rong Shi, North Lake Anju Community Health Service Center, North Lake Anju Community Health Service Center, Nanning 530021, Guangxi Zhuang Autonomous Region, China
Hui Li, Department of Colorectal and Anal Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
Co-first authors: Ke-Jun Wu and Da-Tong Zeng.
Co-corresponding authors: Gang Chen and Hui Li.
Author contributions: Wu KJ and Zeng DT contributed equally to this work as co-first authors; they conducted data collection, performed immunohistochemical staining analysis, and drafted the initial manuscript; Chen G and Li H contributed equally to this work as co-corresponding authors; He RQ and Li DM provided guidance on experimental design, statistical analysis, and manuscript revision; Yao JJ, Liu LM, and Huang WJ performed tissue sample collection, clinical data analysis, and assisted with manuscript preparation; Qin DY conducted computational analysis and assisted with data visualization; Li YF, He H, and Li SD performed laboratory experiments, analyzed results, and contributed to data interpretation; Wen JY and Meng L assisted with patient recruitment, sample handling, and clinical data collection; Shi JR provided technical support and helped with experimental procedures; Chen G conceived and designed the study, supervised all experiments and data analysis, and finalized the manuscript; Li H provided clinical guidance, assisted with result interpretation, and critically reviewed the manuscript.
Supported by the Promoting Project of Basic Capacity for Young and Middle-aged University Teachers in Guangxi, No. 2025KY0164; Youth Science Foundation of Guangxi Medical University, No. GXMUYSF202423; and Guangxi Zhuang Autonomous Region Health Commission Scientific Research Project, No. Z-A20220415 and No. Z20210442.
Institutional review board statement: All patients provided informed consent, and the study was approved by the Yulin Red Cross Hospital Ethics Committee (number: Z20210442).
Conflict-of-interest statement: The authors declare they have no competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Data sharing statement: All data included in this study are available upon request by contact with the corresponding author.
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: Hui Li, MD, PhD, Department of Colorectal and Anal Surgery, The First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Nanning 530021, Guangxi Zhuang Autonomous Region, China.
lihui_gxmu@163.com
Received: April 21, 2025
Revised: May 22, 2025
Accepted: June 10, 2025
Published online: July 24, 2025
Processing time: 92 Days and 18.9 Hours
BACKGROUND
The prevalence of colorectal cancer (CRC) in younger people is increasing. Despite advances in precision medicine, the challenges of drug resistance and high costs persist. Nitidine chloride (NC) has pharmacological potential, and kinesin family member 20A (KIF20A) is overexpressed in various tumors; however, their interaction in CRC remains unexplored.
AIM
To investigate the KIF20A expression characteristics in CRC cells and determine whether it is a potential target gene for NC in inhibiting CRC treatment.
METHODS
Single-cell RNA sequencing (scRNA-seq), spatial transcriptomics, and mRNA expression profiling were used to analyze KIF20A expression in CRC cells. Immunohistochemical staining was used to verify KIF20A expression in 416 clinical samples (208 CRC tissue samples and 208 noncancerous control tissue samples). Clustered regularly interspaced short palindromic repeats (CRISPR) technology was used to evaluate the impact of knocking out KIF20A on CRC cell growth. Molecular docking was applied to analyze NC–KIF20A binding. Finally, RNA sequencing and functional enrichment analysis were performed to explore the mechanism of action of NC in CRC cells.
RESULTS
Treating HCT116 cells with NC was found to significantly downregulate KIF20A (P < 0.05), and the molecular docking analysis revealed high-affinity binding between NC and KIF20A (binding energy = -9.6 kcal/mol). The scRNA-seq, spatial transcriptomics, and mRNA expression profiling results confirmed the significantly high expression of KIF20A in CRC tissues (standardized mean difference = 1.33, 95% confidence interval: 0.885-1.77, summary receiver operating characteristic curve area = 0.94). The immunohistochemical analysis of the clinical samples showed high KIF20A expression in the CRC tissues (P < 0.05), with significant correlation between the level of expression and gender, tumor size, and tumor grade (P < 0.05). Knocking out KIF20A significantly inhibited the growth of various CRC cell lines (CRISPR score < -0.3). The functional enrichment analysis indicated that NC may inhibit CRC by disrupting several biological processes, such as mitotic nuclear division, chromosome segregation, and microtubule binding.
CONCLUSION
Our results indicate that NC binds to KIF20A with high affinity and downregulates its expression in CRC cells, leading to reduced proliferation. Hence, NC has promise as a therapeutic agent in the treatment of CRC, and targeting KIF20A also has potential as a therapeutic strategy. Further KIF20A knockout studies are needed to confirm the binding specificity and mechanistic roles of NC in CRC.
Core Tip: In this study, we identified kinesin family member 20A (KIF20A) as a potential target for nitidine chloride (NC) in colorectal cancer (CRC) cells. Our multi-omics analysis revealed that KIF20A expression was elevated in CRC tissues, particularly in epithelial and proliferative regions, which correlated with clinical parameters. NC treatment significantly downregulated KIF20A in CRC cells, with molecular docking confirming direct binding, and knocking out KIF20A inhibited CRC cell growth. The pathway analysis suggests that NC suppresses CRC by disrupting mitosis, chromosome segregation, and microtubule dynamics by targeting KIF20A.
