Basic Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Feb 15, 2024; 16(2): 398-413
Published online Feb 15, 2024. doi: 10.4251/wjgo.v16.i2.398
Prohibitin 1 inhibits cell proliferation and induces apoptosis via the p53-mediated mitochondrial pathway in vitro
Juan-Juan Shi, Yi-Kai Wang, Mu-Qi Wang, Jiang Deng, Ning Gao, Mei Li, Ya-Ping Li, Xin Zhang, Xiao-Li Jia, Xiong-Tao Liu, Shuang-Suo Dang, Wen-Jun Wang
Juan-Juan Shi, Yi-Kai Wang, Mu-Qi Wang, Jiang Deng, Ning Gao, Mei Li, Ya-Ping Li, Xin Zhang, Xiao-Li Jia, Shuang-Suo Dang, Wen-Jun Wang, Department of Infectious Diseases, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi'an 710004, Shaanxi Province, China
Xiong-Tao Liu, Department of Operating Room, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi'an 710004, Shaanxi Province, China
Co-corresponding authors: Shuang-Suo Dang and Wen-Jun Wang.
Author contributions: Dang SS, Wang WJ, and Shi JJ designed and coordinated the study; Shi JJ, Wang YK, Wang MQ, Gao N, Li M, Zhang X, and Liu XT performed the study; Shi JJ, Wang WJ, Li YP, and Jia XL acquired and analysed the data; Shi JJ wrote the manuscript; all authors were involved in the critical review of the results and have contributed to, read, and approved the final manuscript. Dang SS and Wang WJ contributed equally to this study as co-corresponding authors. There were two reasons for designating Dang SS and Wang WJ as co-corresponding authors. First, the research was performed as a collaborative effort, and the designation of co-corresponding authorship accurately reflects the distribution of responsibilities and burdens associated with the time and effort required to complete the study and the resultant paper. This also ensures effective communication and management of post-submission matters, ultimately enhancing the paper's quality and reliability. Second, Dang SS and Wang WJ contributed efforts of equal substance throughout the research process. The choice of these researchers as co-corresponding authors acknowledges and respects this equal contribution, while recognizing the spirit of teamwork and collaboration of this study.
Supported by the Key Research and Development Program of Shaanxi, No. 2021SF-227 and No. 2020SF-297; and the Natural Science Basic Research Program of Shaanxi, No. 2023-JC-YB-770.
Institutional review board statement: This study was approved by the Institutional Review Board of The Second Affiliated Hospital of Xi’an Jiaotong University and by the Institutional Review Board of the Second Affiliated Hospital of Xi’an Jiaotong University.
Conflict-of-interest statement: The authors have no conflicts of interest to declare.
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: Shuang-Suo Dang, MD, PHD, Professor, Department of Infectious Diseases, The Second Affiliated Hospital of Xi’an Jiaotong University, No. 157 Xiwu Road, Xincheng District, Xi'an 710004, Shaanxi Province, China. dang212@126.com
Received: October 27, 2023
Peer-review started: October 27, 2023
First decision: November 6, 2023
Revised: November 23, 2023
Accepted: January 9, 2024
Article in press: January 9, 2024
Published online: February 15, 2024
Processing time: 98 Days and 7.4 Hours
ARTICLE HIGHLIGHTS
Research background

Prohibitin 1 (PHB1) has been identified as an antiproliferative protein that is highly conserved and ubiquitously expressed, and it participates in a variety of essential cellular functions, including apoptosis, cell cycle control, proliferation, and survival. Emerging evidence indicates that PHB1 may play an important role in the progression of hepatocellular carcinoma (HCC). However, the role of PHB1 in HCC is controversial.

Research motivation

This study aimed to provide a theoretical basis for the use of PHB1 as a possible therapeutic target for liver cancer.

Research objectives

To investigate the effects of PHB1 on cell proliferation, cell cycle progression, and apoptosis in human HCC cells as well as the relevant mechanisms.

Research methods

ELISA, immunohistochemistry, flow cytometry, quantitative real-time PCR, Western blot, and transfection assays were used in this study.

Research results

Low expression of PHB1 was associated with tumour progression in HCC patients. PHB1 inhibited the viability of human HCC cells by arresting the cell cycle. PHB1 induced p53 expression and upregulated Bax expression to activate the mitochondrial signalling pathway, which further enhanced cytochrome C release into the cytosol and activated caspase 9 and caspase 3 to induce apoptosis.

Research conclusions

PHB1 inhibits the viability of human HCC cells by arresting the cell cycle and inducing cell apoptosis via activation of the p53-mediated mitochondrial pathway. Our results revealed a novel mechanism by which PHB1 inhibits HCC and showed that the intrinsic mitochondrial pathway is involved in PHB1 overexpression-induced apoptosis in human HCC cells.

Research perspectives

Although our findings reveal a formerly undescribed function of PHB1 in the induction of apoptosis in human HCC cells, additional studies are needed to understand the precise mechanisms by which PHB1 regulates cell apoptosis.