Huang QL, Zhou SS, Li JD, Xiong DD, He RQ, Huang ZG, Wang L, Tan TM, Dang YW, Mo WJ, Feng ZB, Chen G, Yang ZD. Role of cell cycle-related gene SAC3 domain containing 1 as a potential target of nitidine chloride in hepatocellular carcinoma progression. World J Clin Oncol 2025; 16(5): 104154 [DOI: 10.5306/wjco.v16.i5.104154]
Corresponding Author of This Article
Zhen-Dong Yang, Department of Radiation Oncology, The First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Nanning 530021, Guangxi Zhuang Autonomous Region, China. yangzhendong@stu.gxmu.edu.cn
Research Domain of This Article
Medicine, Research & Experimental
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 Clin Oncol. May 24, 2025; 16(5): 104154 Published online May 24, 2025. doi: 10.5306/wjco.v16.i5.104154
Role of cell cycle-related gene SAC3 domain containing 1 as a potential target of nitidine chloride in hepatocellular carcinoma progression
Qing-Ling Huang, Sheng-Sheng Zhou, Jian-Di Li, Dan-Dan Xiong, Rong-Quan He, Zhi-Guang Huang, Lei Wang, Tian-Ming Tan, Yi-Wu Dang, Wei-Jia Mo, Zhen-Bo Feng, Gang Chen, Zhen-Dong Yang
Qing-Ling Huang, Jian-Di Li, Dan-Dan Xiong, Zhi-Guang Huang, Lei Wang, Tian-Ming Tan, Yi-Wu Dang, Wei-Jia Mo, Zhen-Bo Feng, Gang Chen, Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
Sheng-Sheng Zhou, Rong-Quan He, Department of Medical Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
Zhen-Dong Yang, Department of Radiation Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
Co-first authors: Qing-Ling Huang and Sheng-Sheng Zhou.
Co-corresponding authors: Gang Chen and Zhen-Dong Yang.
Author contributions: Huang QL contributed to writing original draft; Huang QL, Zhou SS, Li JD, Xiong DD and He RQ contributed to methodology and data analysis; Huang ZG, Dang YW and Mo WJ contributed to writing review; Wang L, Tan TM and Feng ZB contributed to data supervision; Yang ZD and Chen G contributed to resources, supervision, writing review and editing; all authors contributed to the study conception and design, have read and approved the final manuscript.
Supported by National Natural Science Foundation of China, No. 82160762 and No. 82460783; Guangxi Medical University “Four New” Project, No. SX202403; Innovation Project of Guangxi Graduate Education, No. JGY2023068; Guangxi Higher Education Undergraduate Teaching Reform Project, No. 2022JGA146; and China Undergraduate Innovation and Entrepreneurship Training Program, No. 202310598045.
Conflict-of-interest statement: The authors did not report a potential conflict of interest.
Data sharing statement: The raw data related to the specific experiment or analysis are available upon request from the corresponding author at chen_gang_triones@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: Zhen-Dong Yang, Department of Radiation Oncology, The First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Nanning 530021, Guangxi Zhuang Autonomous Region, China. yangzhendong@stu.gxmu.edu.cn
Received: December 13, 2024 Revised: March 26, 2025 Accepted: April 17, 2025 Published online: May 24, 2025 Processing time: 158 Days and 4.8 Hours
Abstract
BACKGROUND
Hepatocellular carcinoma (HCC) is at the forefront of the global spectrum of cancer incidence and mortality, with conventional therapies like tyrosine kinase inhibitors limited by resistance. Recent studies have highlighted the promising anticancer effects of nitidine chloride (NC) against HCC. SAC3 domain containing 1 (SAC3D1) is critical for centrosome replication and spindle formation. However, research on SAC3D1 in HCC and NC remains limited.
AIM
To investigate the mechanisms underlying SAC3D1’s role in HCC progression and evaluated its potential as a therapeutic target of NC.
METHODS
RNA sequencing (RNA-seq) identified SAC3D1 expression changes in HCC cells after NC treatment. Molecular docking was further employed to validate the direct binding between NC and SAC3D1. Additionally, HCC multicenter data (The Cancer Genome Atlas_GTEx, ArrayExpress), pathway analysis, Pearson correlation analysis and SAC3D1 in vitro knockdown experiments were integrated to explore the molecular mechanisms underlying SAC3D1's involvement in HCC progression.
RESULTS
RNA-seq showed that NC treatment significantly downregulated SAC3D1 expression [log2(fold change) = - 0.95, P < 0.05], with molecular docking revealing that NC directly bound to SAC3D1 proteins (binding energy: -9.7 kcal/mol). Enrichment analysis showed that most pathways were closely related to the cell cycle. Pearson correlation analysis indicated that SAC3D1 and cell cycle genes were significantly positively correlated(correlation coefficient ≥ 0.3, P < 0.05). SAC3D1 knockdown inhibited HCC cell invasion, migration, and proliferation by arresting cells in the S and G2/M phases. Flow cytometry confirmed that after SAC3D1 knockdown, the early and total apoptosis percentage of HCC cells decreased, while the late apoptosis percentage increased.
CONCLUSION
As a potential target of NC, SAC3D1 may inhibit HCC progression through cell cycle regulation following its downregulation by NC.
Core Tip: The role of SAC3 domain containing 1 (SAC3D1) in hepatocellular carcinoma (HCC) remains unclear. Through bioinformatic analysis, molecular docking techniques, and in vitro experiments, this study demonstrates for the first time that SAC3D1 serves as a novel target for nitidine chloride (NC), which previous studies have shown to have anti-HCC effects. Downregulation of SAC3D1 by NC may inhibit HCC progression by regulating the cell cycle, providing opportunities for novel therapeutic approaches in HCC treatment.
