ArticleAmerican journal of cancer research2025
The ubiquitin ligase RCBTB2 regulates aggrephagy and inhibits prostate cancer progression by targeting GPAA1 for degradation.
Article in American journal of cancer research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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1 citing paper in PubMed.
- RCBTB2 in cancer: context-dependent functions and translational boundaries.Frontiers in oncology · 2026Review
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10 authors.
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Abstract
backgroundProstate cancer (PCa) ranks among the most prevalent malignant tumors affecting the male genitourinary system, presenting a considerable danger to health and human life. Increasing evidence indicates that the ubiquitin-proteasome pathway is essential in both the development and management of PCa.
methodsDifferential expressed genes were screened by integrating the TCGA and GEO databases, and their expression was validated in the HPA dataset. An RCBTB2 overexpression cell line was constructed, and its effects on cellular behavior were analyzed using CCK-8, scratch assay, Transwell, and immunofluorescence staining. A nude mouse model was established to evaluate the tumor-suppressive effects. Furthermore, the interaction between RCBTB2 and GPAA1 was confirmed through multi-omics analysis, co-immunoprecipitation, and immunofluorescence co-localization experiments. GPAA1 knockdown cell lines were then constructed to observe changes in cellular phenotypes.
resultsThe expression of RCBTB2 was significantly negatively correlated with the malignancy of PCa. Overexpression of RCBTB2 notably inhibited DU145 cell proliferation, migration, invasion, and EMT, as well as reduced the growth of xenograft tumors in nude mice. Multi-omics analysis revealed that RCBTB2 promoted the ubiquitin-mediated degradation of GPAA1 (protein downregulation without changes in mRNA levels), and experiments confirmed their direct interaction. Furthermore, GPAA1 knockdown suppressed the malignant biological behaviors of PCa cells and reduced the expression of aggrephagy-related factors such as p62.
conclusionThis study for the first time unveils the molecular mechanism by which RCBTB2 inhibits PCa progression through ubiquitination-mediated degradation of GPAA1. It provides a novel target for protein homeostasis-based therapy, with promising clinical value.
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