Basic Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Mar 15, 2024; 16(3): 1006-1018
Published online Mar 15, 2024. doi: 10.4251/wjgo.v16.i3.1006
Ubiquitin-specific protease 21 promotes tumorigenicity and stemness of colorectal cancer by deubiquitinating and stabilizing ZEB1
Jun-Jun Lin, Ye-Cai Lu
Jun-Jun Lin, Ye-Cai Lu, Department of Gastrointestinal Surgery, Chaohu Hospital of Anhui Medical University, Chaohu 238000, Anhui Province, China
Author contributions: Lin JJ wrote the manuscript; Lin JJ and Lu YC collected and analyzed the data; all authors read and approved the final manuscript.
Supported by Anhui Provincial Health Research Project, No. AHWJ2022c036.
Institutional review board statement: This study was approved by the Ethics Committee of Chaohu Hospital of Anhui Medical University (No. KYXM-2022-10-011).
Institutional animal care and use committee statement: The Animal Care and Use Committee of Beijing Viewsolid Biotechnology Co. LTD approved this work (No. VS2126A00153).
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: All the data used to support the findings of this study are included within the article.
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: Ye-Cai Lu, MD, Professor, Department of Gastrointestinal Surgery, Chaohu Hospital of Anhui Medical University, No. 64 Chaohu North Road, Chaohu 238000, Anhui Province, China. 13965691202@163.com
Received: October 26, 2023
Peer-review started: October 26, 2023
First decision: December 31, 2023
Revised: January 4, 2024
Accepted: January 31, 2024
Article in press: January 31, 2024
Published online: March 15, 2024
Processing time: 138 Days and 1 Hours
Abstract
BACKGROUND

Colorectal cancer (CRC) is one very usual tumor together with higher death rate. Ubiquitin-specific protease 21 (USP21) has been confirmed to take part into the regulation of CRC progression through serving as a facilitator. Interestingly, the promotive function of USP21 has also discovered in the progression of CRC. ZEB1 has illustrated to be modulated by USP7, USP22 and USP51 in cancers. However, the regulatory functions of USP21 on ZEB1 in CRC progression need more investigations.

AIM

To investigate the relationship between USP21 and ZEB1 in CRC progression.

METHODS

The mRNA and protein expressions were assessed through RT-qPCR, western blot and IHC assay. The interaction between USP21 and ZEB1 was evaluated through Co-IP and GST pull down assays. The cell proliferation was detected through colony formation assay. The cell migration and invasion abilities were determined through Transwell assay. The stemness was tested through sphere formation assay. The tumor growth was evaluated through in vivo mice assay.

RESULTS

In this work, USP21 and ZEB1 exhibited higher expression in CRC, and resulted into poor prognosis. Moreover, the interaction between USP21 and ZEB1 was further investigated. It was demonstrated that USP21 contributed to the stability of ZEB1 through modulating ubiquitination level. In addition, USP21 strengthened cell proliferation, migration and stemness through regulating ZEB1. At last, through in vivo assays, it was illustrated that USP21/ZEB1 axis aggravated tumor growth.

CONCLUSION

For the first time, these above findings manifested that USP21 promoted tumorigenicity and stemness of CRC by deubiquitinating and stabilizing ZEB1. This discovery suggested that USP21/ZEB1 axis may provide novel sights for the treatment of CRC.

Keywords: Ubiquitin-specific protease 21; ZEB1; Stemness; Colorectal cancer

Core Tip: Ubiquitin-specific protease 21 (USP21) and ZEB1 had been discovered to exhibit higher expressions in colorectal cancer (CRC) tissues and cells, and result into poor prognosis. USP21 contributed to the stability of ZEB1 through modulating ubiquitination level. Our findings proved that USP21 promoted tumorigenicity and stemness of CRC by deubiquitinating and stabilizing ZEB1. Moreover, it was uncovered that USP21/ZEB1 axis aggravated tumor growth in vivo.