Basic Study
Copyright ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Jun 15, 2025; 17(6): 106080
Published online Jun 15, 2025. doi: 10.4251/wjgo.v17.i6.106080
Regulator of chromosome condensation 1 promotes hepatocellular carcinoma proliferation via cell-division-cycle-associated-8 dependent phosphoinositide 3-kinase/protein kinase B signaling
Ya-Tao Wang, Yu-Le Yong, Ze-Kun Liu, Yi-Xuan Shen, Xiang-Min Yang, Zhi-Nan Chen
Ya-Tao Wang, Yu-Le Yong, Ze-Kun Liu, Yi-Xuan Shen, Xiang-Min Yang, Zhi-Nan Chen, Department of Cell Biology, National Translational Science Center for Molecular Medicine, The Fourth Military Medical University, Xi’an 710032, Shaanxi Province, China
Co-first authors: Ya-Tao Wang and Yu-Le Yong.
Co-corresponding authors: Xiang-Min Yang and Zhi-Nan Chen.
Author contributions: Wang YT and Yong YL performed all the experiments, and drafted the manuscript, they contributed equally to this article, they are the co-first authors of this manuscript; Wang YT and Liu ZK conducted the bioinformatics analyses; Wang YT, Yong YL, Liu ZK, and Shen YX analyzed the data, interpreted the results of the experiments, and prepared the figures and tables; Chen ZN and Yang XM conceived and designed the study, they contributed equally to this article, they are the co-corresponding authors of this manuscript; and all authors have read and agreed to the published version of the manuscript.
Supported by the National Natural Science Foundation of China, No. 82002940 and No. 82203336; and Shaanxi Natural Science Foundation, No. 2023-JC-YB-166.
Institutional review board statement: This study was approved by the Medical Ethics Committee of Shanghai Outdo Biotech Company, approval No. SHYJS-CP-1804017.
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: Zhi-Nan Chen, PhD, Professor, Department of Cell Biology, National Translational Science Center for Molecular Medicine, The Fourth Military Medical University, No. 169 Changle West Road, Xi’an 710032, Shaanxi Province, China. znchen@fmmu.edu.cn
Received: February 17, 2025
Revised: April 1, 2025
Accepted: April 18, 2025
Published online: June 15, 2025
Processing time: 118 Days and 21.4 Hours
Abstract
BACKGROUND

Hepatocellular carcinoma (HCC) ranks among the most prevalent and deadly malignancies, characterized by a high recurrence rate. Regulator of chromosome condensation 1 (RCC1) serves as a principal guanine nucleotide exchange factor for ras-related nuclear protein guanosine triphosphatase (GTPase) and is implicated in various cancers. However, the role of RCC1 in HCC remains unexplored.

AIM

To elucidate the functional significance and molecular mechanisms of RCC1 in HCC.

METHODS

Bioinformatics were to examine the expression levels of RCC1 in HCC and to assess its impact on the prognosis of this malignancy. The cell counting kit-8 assay and flow cytometry were utilized to evaluate the cell viability and cell cycle of HCC cells. Furthermore, quantitative reverse transcription and immunoblotting were to investigate the influence of RCC1 on cyclin associated proteins.

RESULTS

Bioinformatics analysis revealed that RCC1 was highly expressed in HCC and correlated with poor prognosis in HCC patients. Functional studies showed that RCC1 overexpression promoted the malignant phenotype of HCC cells, especially the proliferation of HCC cells, whereas RCC1 knockdown had the opposite effect. Mechanistically, we identified cell division cycle-associated (CDCA) 8 as a downstream target of RCC1 in HCC. RCC1 overexpression markedly increased CDCA8 levels, consequently enhancing cell proliferation and survival in HCC cells. Additionally, we discovered that RCC1 contributed to the development and progression of HCC by activating the phosphoinositide 3-kinase/protein kinase B/cyclin-dependent kinase inhibitor 1a pathway through CDCA8.

CONCLUSION

Our study provides profound insights into the pivotal role of RCC1 in HCC and its potential as a therapeutic target.

Keywords: Hepatocellular carcinoma; Regulator of chromosome condensation 1; Proliferation; Cell cycle; Cell division cycle-associated 8; Phosphoinositide 3-kinase/protein kinase B pathway

Core Tip: In this study, we investigated the role of regulator of chromosome condensation 1 (RCC1) in promoting the proliferation of hepatocellular carcinoma (HCC) cells. Initially, we determined that RCC1 is significantly upregulated in HCC and correlates with poor prognosis. Subsequently, we demonstrated that RCC1 facilitates the G1/S phase transition by regulating cell division cycle-associated 8. Furthermore, our findings indicate that the RCC1/cycle-associated 8 axis promotes HCC proliferation via the phosphoinositide 3-kinase/protein kinase B/cyclin-dependent kinase inhibitor 1a signaling pathway. Collectively, this research elucidates the association between RCC1 and HCC and highlights the role of RCC1 in regulating the G1/S transition of the cell cycle.