Basic Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Feb 14, 2024; 30(6): 565-578
Published online Feb 14, 2024. doi: 10.3748/wjg.v30.i6.565
Role of deubiquitinase JOSD2 in the pathogenesis of esophageal squamous cell carcinoma
Wen-Peng Wang, Dan Shi, Duo Yun, Jun Hu, Jie-Fu Wang, Jia Liu, Yan-Peng Yang, Ming-Rui Li, Jun-Feng Wang, Da-Lu Kong
Wen-Peng Wang, Jun Hu, Jie-Fu Wang, Jia Liu, Yan-Peng Yang, Jun-Feng Wang, Da-Lu Kong, Department of Colorectal Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin’s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China
Dan Shi, Department of Gastrointestinal Surgery, Tianjin Nan Kai Hospital, Tianjin Medical University, Tianjin Key Laboratory of Acute Abdomen Disease Associated Organ Injury and ITCWM Repair, Institute of Integrative Medicine for Acute Abdominal Diseases, Tianjin 300100, China
Duo Yun, Department of Oncology, The First Hospital of Hohhot, Hohhot 010000, Inner Mongolia Autonomous Region, China
Ming-Rui Li, Department of Endocrinology, Dazhou Central Hospital, Dazhou 635000, Sichuan Province, China
Co-first authors: Wen-Peng Wang and Dan Shi.
Co-corresponding authors: Jun-Feng Wang and Da-Lu Kong.
Author contributions: Wang WP and Shi D contributed equally to this work; Kong DL and Wang JF were co-corresponding authors; The study was conceptualized and designed by Kong DL, Wang JF, and Wang WP; Shi D and Yun D were in charge of acquiring public data; Bioinformatic and statistical analyses were conducted by Wang WP, Shi D, Yun D, Hu J, Wang JF, and Liu J; Wang WP, Shi D, Yun D, Yang YP, and Li MR carried out both in vitro and in vivo experiments; Figures and tables were prepared, and the initial draft of the manuscript was written by Wang WP, Shi D, Wang JF and Yun D; Manuscript revisions were performed by Kong DL, Wang JF, and Wang WP; All authors have reviewed and approved the final version of the manuscript for publication.
Supported by Tianjin Key Medical Discipline (Specialty) Construction Project, No. TJYXZDXK-009A; Tianjin Medical University Cancer Hospital National Natural Science Foundation Cultivation Program, No. 220108; National Natural Science Foundation of China, No. 82373134; Science and Technology Development Fund of Tianjin Education Commission for Higher Education, No. 2022KJ228; Chinese Anti-Cancer Association-Heng Rui Anti-angiogenesis Targeted Tumor Research Fund, No. 2021001045; and Scientific Research Translational Foundation of Wenzhou Safety (Emergency) Institute of Tianjin University, No. TJUWYY2022025.
Institutional review board statement: The study was reviewed and approved by the Institutional Review Board of Tianjin Medical University Cancer Institute and Hospital, No. Ek2023018.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Tianjin Cancer Institute Animal Ethics Committee, No. NSFC-AE-2023n2.
Informed consent statement: All study participants or their legal guardian provided informed written consent about personal and medical data collection prior to study enrolment.
Conflict-of-interest statement: The authors declare no conflict of interest.
Data sharing statement: The data used and/or analyzed during the current study are available from the corresponding author on reasonable request.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
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: Da-Lu Kong, BMed, Chief Physician, Director, Doctor, Department of Colorectal Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin’s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Huanhuxi Road, Hexi District, Tianjin 300060, China. kongdalu2021@126.com
Received: December 4, 2023
Peer-review started: December 4, 2023
First decision: December 8, 2023
Revised: December 20, 2023
Accepted: January 16, 2024
Article in press: January 16, 2024
Published online: February 14, 2024
Processing time: 62 Days and 22.2 Hours
Core Tip

Core Tip: JOSD2, a deubiquitinating enzyme, is a key player in the aggressive pathogenesis of esophageal squamous cell carcinoma (ESCC). Elevated JOSD2 expression in ESCC tissues is associated with poor prognosis. Functional analyses, including in vivo xenograft assays, highlight JOSD2's role in promoting tumor proliferation and drug resistance. Mechanistically, JOSD2 activates the MAPK/ERK and PI3K/AKT signaling pathways. Mass spectrometry identified key interacting proteins, including USP47, IGKV2D-29, HSP90AB1, and PRMT5. This study underscores the potential role of JOSD2 as a therapeutic target in ESCC.