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©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
Exploring the potential function of high expression of ANAPC1 in regulating ubiquitination in hepatocellular carcinoma
Yu-Xing Tang, Wei-Zi Wu, Sheng-Sheng Zhou, Da-Tong Zeng, Guang-Cai Zheng, Rong-Quan He, Di-Yuan Qin, Wan-Ying Huang, Ji-Tian Chen, Yi-Wu Dang, Yu-Lu Tang, Bang-Teng Chi, Yan-Ting Zhan, Gang Chen
Yu-Xing Tang, Wan-Ying Huang, Yi-Wu Dang, Yu-Lu Tang, Bang-Teng Chi, Yan-Ting Zhan, Gang Chen, Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
Wei-Zi Wu, Ji-Tian Chen, Department of Pathology, People’s Hospital of Ling Shan, Nanning 535400, 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
Da-Tong Zeng, Department of Pathology, Redcross Hospital of Yulin City, Nanning 537000, Guangxi Zhuang Autonomous Region, China
Guang-Cai Zheng, Department of Hepatobiliary Surgery, Redcross Hospital of Yulin City, Nanning 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
Co-first authors: Yu-Xing Tang and Wei-Zi Wu.
Co-corresponding authors: Yan-Ting Zhan and Gang Chen.
Author contributions: All authors contributed to the conception and design of this study; Zhou SS, Zheng GC, He RQ, Qin DY, Huang WY, Chen JT, Dang YW, Tang YL, Zhan YT and Chen G conceived and designed the study and guided the experimental operations; Tang YX and Wu WZ conducted the necessary experiments; Tang YX collected and analyzed the data; Tang YX, Wu WZ, Zeng DT, Chi BT drafted the manuscript; He RQ, Zhan YT and Chen G supervised the data analysis; Wu WZ, Zhou SS, Zheng GC, He RQ, Qin DY, Huang WY, Chen JT, Dang YW, Tang YL, Zhan YT and Chen G reviewed and revised the scientific content of the manuscript; All authors read and approved the final manuscript.
Supported by the National Natural Science Foundation of China, No. NSFC82160762 and No. NSFC82460783; Innovation Project of Guangxi Graduate Education, No. JGY2023068; Guangxi Higher Education Undergraduate Teaching Reform Project, No. 2022JGA146; Guangxi Zhuang Autonomous Region Health Commission Scientific Research Project, No. Z-A20220469; Future Academic Star of Guangxi Medical University, No. WLXSZX24074; and the China Undergraduate Innovation and Entrepreneurship Training Program, No. X202410598360.
Institutional review board statement: The Ethics Committee of the First Affiliated Hospital of Guangxi Medical University (No. 2022-KT-GuiWei-074), Lingshan County People’s Hospital (No. Z2090523) and the Red Cross Hospital of Yulin City (No. 2024-8) approved the study.
Institutional animal care and use committee statement: This study did not involve animal experiments.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
Data sharing statement: Dataset available from the corresponding author at
chengang@gxmu.edu.cn. Participants gave informed consent for data sharing.
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: Gang Chen, MD, Professor, Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Nanning 530021, Guangxi Zhuang Autonomous Region, China.
chengang@gxmu.edu.cn
Received: November 25, 2024
Revised: January 22, 2025
Accepted: March 14, 2025
Published online: May 15, 2025
Processing time: 172 Days and 0.1 Hours
BACKGROUND
ANAPC1, a key regulator of the ubiquitination in tumour development, has not been thoroughly studied in hepatocellular carcinoma (HCC).
AIM
To elucidate the expression of ANAPC1 in HCC and its potential regulatory mechanism related to ubiquitination.
METHODS
Bulk RNA (RNA sequencing and microarrays), immunohistochemistry (IHC) tissues, and single-cell RNA sequencing (scRNA-seq) data were integrated to comprehensively investigate ANAPC1 expression in HCC. Clustered regularly interspaced short palindromic repeats analysis was performed to assess growth in HCC cell lines following ANAPC1 knockout. Enrichment analyses were conducted to explore the functions of ANAPC1. ScRNA-seq data was used to examine the cell cycle and metabolic levels. CellChat analysis was applied to investigate the interactions between ANAPC1 and different cell types. The relationship between ANAPC1 expression and drug concentration was analyzed.
RESULTS
ANAPC1 messenger RNA was found to be upregulated in bulk RNA, IHC tissues samples and malignant hepatocytes. The proliferation of JHH2 cell lines was most significantly inhibited after ANAPC1 knockdown. In biological pathways, the development of HCC was found to be linked to the regulation of ubiquitin-mediated proteolysis. Additionally, scRNA-seq results indicated that highly expressed ANAPC1 was in the G2/M phase, with increased glycolysis/gluconeogenesis activity. A CellChat analysis showed that ANAPC1 was associated with the regulation of the migration inhibitory factor-(cluster of differentiation 74 + C-X-C chemokine receptor type 4) pathway. Higher ANAPC1 expression correlated with stronger effects of sorafenib, dasatinib, ibrutinib, lapatinib, nilotinib and afatinib.
CONCLUSION
The high expression level of ANAPC1 may regulate the cell cycle and metabolic levels of HCC through the ubiquitination-related pathway, thereby promoting disease progression.
Core Tip: ANAPC1, a key ubiquitination regulator in tumours, remains unstudied in hepatocellular carcinoma (HCC). This first multicenter study on ANAPC1 in HCC shows its high expression in bulk RNA (n = 3913, including RNA sequencing and microarray), immunohistochemistry (n = 632) and single-cell RNA sequencing (15999 malignant hepatocytes). Clustered regularly interspaced short palindromic repeats knockout of ANAPC1 inhibited HCC cell proliferation. Gene set enrichment analysis, gene ontology and Kyoto encyclopedia of genes and genomes analyses revealed the role of the high expression of ANAPC1 in ubiquitin-mediated protein degradation, which may affect the G2/M phase and glycolysis, regulate migration inhibitory factor signalling and enhance HCC sensitivity to sorafenib, dasatinib, ibrutinib, lapatinib, nilotinib and afatinib.
