{"title":"UCHL3: a crucial deubiquitinase in DNA damage repair and tumor progression.","authors":"Jiahao Liu, Shulu Hu, Junqi Xiao, Jumei Zhou","doi":"10.1186/s12935-025-03884-x","DOIUrl":null,"url":null,"abstract":"<p><p>Ubiquitin carboxyl terminal hydrolase L3 (UCHL3) is a deubiquitinase belonging to UCH protease family. Previous studies have demonstrated that abnormal expression of UCHL3 is correlated with the development of human diseases, especially in tumors. Notably, UCHL3 exhibits contradictory biological functions across different cancer types. Initial studies identified UCHL3 as a tumor suppressor in prostate cancer. However, emerging evidence suggests that UCHL3 serves as an oncogene in other cancers. Several UCHL3 inhibitors have shown a promising anti-tumor effect in vitro and in vivo. UCHL3 has also been linked to DNA damage repair, which is essential for genome stability. Overexpression of UCHL3 enhances DNA damage repair induced resistance to chemotherapy or radiotherapy in certain tumor types. This review aims to summarize the promoting role of UCHL3 in DNA damage repair and its dual, paradoxical roles in tumor progression, along with the associated mechanisms, and to provide insights into the use of UCHL3 as a therapeutic target for overcoming DNA damage repair-mediated resistance to chemotherapy and radiotherapy, as well as for treating tumors.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"276"},"PeriodicalIF":6.0000,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12278599/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer Cell International","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s12935-025-03884-x","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Ubiquitin carboxyl terminal hydrolase L3 (UCHL3) is a deubiquitinase belonging to UCH protease family. Previous studies have demonstrated that abnormal expression of UCHL3 is correlated with the development of human diseases, especially in tumors. Notably, UCHL3 exhibits contradictory biological functions across different cancer types. Initial studies identified UCHL3 as a tumor suppressor in prostate cancer. However, emerging evidence suggests that UCHL3 serves as an oncogene in other cancers. Several UCHL3 inhibitors have shown a promising anti-tumor effect in vitro and in vivo. UCHL3 has also been linked to DNA damage repair, which is essential for genome stability. Overexpression of UCHL3 enhances DNA damage repair induced resistance to chemotherapy or radiotherapy in certain tumor types. This review aims to summarize the promoting role of UCHL3 in DNA damage repair and its dual, paradoxical roles in tumor progression, along with the associated mechanisms, and to provide insights into the use of UCHL3 as a therapeutic target for overcoming DNA damage repair-mediated resistance to chemotherapy and radiotherapy, as well as for treating tumors.
期刊介绍:
Cancer Cell International publishes articles on all aspects of cancer cell biology, originating largely from, but not limited to, work using cell culture techniques.
The journal focuses on novel cancer studies reporting data from biological experiments performed on cells grown in vitro, in two- or three-dimensional systems, and/or in vivo (animal experiments). These types of experiments have provided crucial data in many fields, from cell proliferation and transformation, to epithelial-mesenchymal interaction, to apoptosis, and host immune response to tumors.
Cancer Cell International also considers articles that focus on novel technologies or novel pathways in molecular analysis and on epidemiological studies that may affect patient care, as well as articles reporting translational cancer research studies where in vitro discoveries are bridged to the clinic. As such, the journal is interested in laboratory and animal studies reporting on novel biomarkers of tumor progression and response to therapy and on their applicability to human cancers.