title: The Arkadia-ESRP2 axis suppresses tumor progression: analyses in clear-cell renal cell carcinoma.
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.
authors.affiliation: Department of Molecular Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.|Division of Molecular Biotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Ariake, Koto-ku, Tokyo, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Mizutani
authors.affiliation: Department of Molecular Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: D
authors.initials: D
authors.lastname: Koinuma
authors.affiliation: Division of Molecular Biotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Ariake, Koto-ku, Tokyo, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Seimiya
authors.affiliation: Department of Molecular Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Miyazono
mesh_terms: D017398:Alternative Splicing; D015153:Blotting, Western; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D018450:Disease Progression; D004847:Epithelial Cells / Q000378:metabolism; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D063990:Gene Ontology; D057809:HEK293 Cells; D006801:Humans; D053208:Kaplan-Meier Estimate; D007680:Kidney Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D061986:MCF-7 Cells; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D011379:Prognosis; D011485:Protein Binding; D034622:RNA Interference; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D044767:Ubiquitin-Protein Ligases / Q000235:genetics* / Q000378:metabolism; D054875:Ubiquitination
chemical_list: C539365:ESRP2 protein, human; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; C486067:RNF111 protein, human; D044767:Ubiquitin-Protein Ligases