Dataset Information

BAP1 maintains chromosome stability by stabilizing DIDO1 in renal cell carcinoma.

ABSTRACT: BRCA1-associated protein 1 (BAP1) is a member of the ubiquitin C-terminal hydrolase family of deubiquitinating enzymes and is implicated in transcriptional regulation. The BAP1 gene is mutated in 5%-15% of patients with clear cell renal cell carcinoma (ccRCC), the most common form of renal cancer, which suggests that BAP1 is a tumor suppressor. However, whether BAP1 influences the progression of ccRCC tumors expressing wildtype (WT) BAP1 is unclear. Here, we identified DIDO1 as a bona fide substrate for BAP1. DIDO1 is a component of the centrosome proteins and plays an essential role in spindle assembly. BAP1 binds to DIDO1 and stabilizes DIDO1 through de-ubiquitination. BAP1 contributes to chromosome stability partially via DIDO1. A positive correlation was identified between BAP1 and DIDO1 expression in ccRCC tissues. Downregulation of both BAP1-loss and DIDO1 protein expression in ccRCC was associated with adverse clinicopathological features. This study revealed a novel mechanism involving BAP1 in the regulation of DIDO1 stability, and the results also provide insight into the relationship between BAP1 mutations and chromosome instability in ccRCC.

SUBMITTER: Xiao J

PROVIDER: S-EPMC7269789 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

BAP1 maintains chromosome stability by stabilizing DIDO1 in renal cell carcinoma.

Xiao Jiantao J Zhang Ruhan R Peng Jingtao J Yang Zhonghua Z

American journal of cancer research 20200501 5

BRCA1-associated protein 1 (BAP1) is a member of the ubiquitin C-terminal hydrolase family of deubiquitinating enzymes and is implicated in transcriptional regulation. The <i>BAP1</i> gene is mutated in 5%-15% of patients with clear cell renal cell carcinoma (ccRCC), the most common form of renal cancer, which suggests that BAP1 is a tumor suppressor. However, whether BAP1 influences the progression of ccRCC tumors expressing wildtype (WT) BAP1 is unclear. Here, we identified DIDO1 as a bona fid ...[more]

PMID: 32509391

Similar Datasets

Project description:Background: Clear cell renal cell carcinoma (ccRCC) is the most prevalent histologic subtype of kidney cancers in adults, which could be divided into two distinct subgroups according to the BRCA1 associated protein-1 (BAP1) mutation status. In the current study, we comprehensively analyzed the genome-wide microRNA (miRNA) expression profiles in ccRCC, with the aim to identify the differentially expressed miRNAs between BAP1 mutant and wild-type tumors, and generate a BAP1 mutation-specific miRNA signature for ccRCC patients with wild-type BAP1. Methods: The BAP1 mutation status and miRNA profiles in BAP1 mutant and wild-type tumors were analyzed. Subsequently, the association of the differentially expressed miRNAs with patient survival was examined, and a BAP1 mutation-specific miRNA signature was generated and examined with Kaplan-Meier survival, univariate and multivariate Cox regression analyses. Finally, the bioinformatics methods were adopted for the target prediction of selected miRNAs and functional annotation analyses. Results: A total of 350 treatment-naïve primary ccRCC patients were selected from The Cancer Genome Atlas project, among which 35 (10.0%) subjects carried mutant BAP1 and had a shorter overall survival (OS) time. Furthermore, 33 miRNAs were found to be differentially expressed between BAP1 mutant and wild-type tumors, among which 11 (miR-149, miR-29b-2, miR-182, miR-183, miR-21, miR-365-2, miR-671, miR-365-1, miR-10b, miR-139, and miR-181a-2) were significantly associated with OS in ccRCC patients with wild-type BAP1. Finally, a BAP1 mutation-specific miRNA signature consisting of 11 miRNAs was generated and validated as an independent prognostic parameter. Conclusions: In summary, our study identified a total of 33 miRNAs differentially expressed between BAP1 mutant and wild-type tumors, and generated a BAP1 mutation-specific miRNA signature including eleven miRNAs, which could serve as a novel prognostic biomarker for ccRCC patients with wild-type BAP1.

Dataset Information

BAP1 maintains chromosome stability by stabilizing DIDO1 in renal cell carcinoma.

Publications

BAP1 maintains chromosome stability by stabilizing DIDO1 in renal cell carcinoma.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets