RRC ID 63391
Author Mizutani A, Koinuma D, Seimiya H, Miyazono K.
Title The Arkadia-ESRP2 axis suppresses tumor progression: analyses in clear-cell renal cell carcinoma.
Journal Oncogene
Abstract Tumor-specific alternative splicing is implicated in the progression of cancer, including clear-cell renal cell carcinoma (ccRCC). Using ccRCC RNA sequencing data from The Cancer Genome Atlas, we found that epithelial splicing regulatory protein 2 (ESRP2), one of the key regulators of alternative splicing in epithelial cells, is expressed in ccRCC. ESRP2 mRNA expression did not correlate with the overall survival rate of ccRCC patients, but the expression of some ESRP-target exons correlated with the good prognosis and with the expression of Arkadia (also known as RNF111) in ccRCC. Arkadia physically interacted with ESRP2, induced polyubiquitination and modulated its splicing function. Arkadia and ESRP2 suppressed ccRCC tumor growth in a coordinated manner. Lower expression of Arkadia correlated with advanced tumor stages and poor outcomes in ccRCC patients. This study thus reveals a novel tumor-suppressive role of the Arkadia-ESRP2 axis in ccRCC.
Volume 35(27)
Pages 3514-23
Published 2016-7-7
DOI 10.1038/onc.2015.412
PII onc2015412
PMID 26522722
PMC PMC5399154
MeSH Alternative Splicing Blotting, Western Carcinoma, Renal Cell / genetics* Carcinoma, Renal Cell / metabolism Carcinoma, Renal Cell / pathology Cell Line, Tumor Cell Proliferation / genetics Disease Progression Epithelial Cells / metabolism Gene Expression Profiling / methods Gene Expression Regulation, Neoplastic Gene Ontology HEK293 Cells Humans Kaplan-Meier Estimate Kidney Neoplasms / genetics* Kidney Neoplasms / metabolism Kidney Neoplasms / pathology MCF-7 Cells Nuclear Proteins / genetics* Nuclear Proteins / metabolism Prognosis Protein Binding RNA Interference RNA-Binding Proteins / genetics* RNA-Binding Proteins / metabolism Reverse Transcriptase Polymerase Chain Reaction Ubiquitin-Protein Ligases / genetics* Ubiquitin-Protein Ligases / metabolism Ubiquitination
IF 7.971
Human and Animal Cells OS-RC-2(RCB0735)