Ubiquitin-specific peptidases in lymphoma: a path to novel therapeutics

Maryam Samareh Salavatipour; Shirin Tavakoli; Aram Halimi; Shima Tavoosi; Amir-Hossein Baghsheikhi; Abdolkarim Talebi-Taheri; Mehdi Niloufari; Zahra Salehi; Javad Verdi; Soheila Rahgozar; Alireza Mosavi-Jarrahi; Mohammad Ahmadvand

doi:10.3389/fphar.2024.1356634

Ubiquitin-specific peptidases in lymphoma: a path to novel therapeutics

Front Pharmacol. 2024 Nov 27:15:1356634. doi: 10.3389/fphar.2024.1356634. eCollection 2024.

Authors

Affiliations

¹ Department of Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.
² Department of Epidemiology, School of Public Health and Safety, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
³ Research Center for Social Determinants of Health, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
⁴ Department of Cell and Molecular Biology and Microbiology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan, Iran.
⁵ Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran.
⁶ Student Research Committee, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
⁷ Shahid Beheshti University of Medical Sciences, Tehran, Iran.
⁸ Hematology, Oncology and Stem Cell Transplantation Research Center, Research Institute for Oncology, Hematology and Cell Therapy, Tehran University of Medical Sciences, Tehran, Iran.
⁹ Cancer Research Centre, Shahid Beheshti University of Medical Sciences, Tehran Iran.
¹⁰ Cell Therapy and Hematopoietic Stem Cell Transplantation Research Center, Research Institute for Oncology, Hematology, and Cell Therapy, Tehran University of Medical Sciences, Tehran, Iran.

^# Contributed equally.

Abstract

Background: Ubiquitin-specific peptidases (USPs), also known as deubiquitinating enzymes (DUBs), play a crucial role in maintaining cellular homeostasis by selectively removing ubiquitin molecules from targeted proteins. This process affects protein stability, subcellular localization, and activity, thereby influencing processes such as DNA repair, cell cycle regulation, and apoptosis. Abnormal USP activities have been linked to various diseases, including cancer. Emerging evidence in lymphoma studies highlights the significance of USPs in controlling signaling pathways related to cancer initiation and progression and presents them as potential therapeutic targets.

Aim: This study aimed to elucidate the multifaceted roles of USPs in lymphoma.

Methods: This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Articles published in English up to May 2023 were retrieved from PubMed, Web of Science, and Scopus. The inclusion criteria focused on studies investigating the role of USPs in lymphoma cancer, involving human subjects or relevant lymphoma cell lines, exploring molecular mechanisms and signaling pathways, and assessing diagnostic or prognostic value.

Results: After the selection process, 23 studies were selected for analysis. USPs were found to affect various aspects of lymphoma development and progression. Specific USPs were identified with roles in cell-cycle regulation, apoptosis modulation, drug resistance, DNA repair, and influence of key oncogenic pathways, such as B cell receptor (BCR) signaling.

Conclusion: This systematic review underscores the emerging role of USPs in lymphoma and their potential as therapeutic targets. Inhibitors of USPs, such as USP14 inhibitors, show promise in overcoming drug resistance. The dynamic interplay between USPs and lymphoma biology presents an exciting opportunity for future research and the development of more effective treatments for patients with lymphoma. Understanding the intricate functions of USPs in lymphoma offers new insights into potential therapeutic strategies, emphasizing the significance of these enzymes in the context of cancer biology.

Keywords: Hodgkin; USPs; cancer; lymphoma; non-Hodgkin; ubiquitin-specific peptidases.

Publication types

Systematic Review

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This study was funded partially by the Shahid Beheshti University of Medical Sciences, Tehran, Iran (grant number: 43005899).