Regulation of tumor-specific alternative splicing

2015 Fiscal Year Final Research Report

• Project/Area Number: 26830066
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Tumor biology
• Research Institution: Japanese Foundation for Cancer Research
• Principal Investigator: MIZUTANI Anna 公益財団法人がん研究会, がん化学療法センター分子生物治療研究部, 研究員 (30615159)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Keywords: スプライシング / 明細胞型腎細胞がん / ユビキチン化 / タンパク質機能制御

Outline of Final Research Achievements

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 in ccRCC. Arkadia physically interacted with ESRP2, induced polyubiquitination and modulates 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 reveals a novel tumor-suppressive role of the Arkadia-ESRP2 axis in ccRCC.

Free Research Field

分子病理学