MP49-04 CRITICAL ROLES OF A NUCLEOLAR PROTEIN DDX31 IN BLADDER CARCINOGENESIS DEPENDING ON P53 MUTATION STATUS.

Abstract

You have accessJournal of UrologyBladder Cancer: Basic Research III1 Apr 2015MP49-04 CRITICAL ROLES OF A NUCLEOLAR PROTEIN DDX31 IN BLADDER CARCINOGENESIS DEPENDING ON P53 MUTATION STATUS. Kei Daizumoto, Tomoya Fukawa, Hisanori Uehara, Toyomasa Katagiri, and Hiro-omi Kanayama Kei DaizumotoKei Daizumoto More articles by this author , Tomoya FukawaTomoya Fukawa More articles by this author , Hisanori UeharaHisanori Uehara More articles by this author , Toyomasa KatagiriToyomasa Katagiri More articles by this author , and Hiro-omi KanayamaHiro-omi Kanayama More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.508AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Bladder cancer (BCa) is the second common genitourinary tumor, yet the detailed mechanisms of its carcinogenesis is largely unknown. We previously identified that a novel nucleolar protein DDX31 (DEAD box polypeptide 31) contribute renal cell carcinoma (RCC) oncogenesis through its regulating the p53-MDM2 pathway, indicating a new mechanism of p53 inactivation in RCC cells. On the other hand, we also found frequent up-regulation of DDX31 in BCa although p53 mutations often occur. In this study, we report the distinct critical roles of DDX31 in bladder carcinogenesis, especially cancer progression. METHODS To investigate the significance of the DDX31 upregulation in BCa, we conducted immunohistochemical staining of 71 BCa specimens with the anti-DDX31 antibody, and estimated the association of DDX31 expression levels on the stained tissues based on a scoring method with cancer-disease specific survival by the Kaplan-Meier method and the log rank test. Next, we examined the siRNA mediated-knockdown effect of DDX31 expression on proliferation, migration and invasion abilities by MTT, wound healing and matrigel invasion assays. Moreover, to investigate biological function of DDX31, we examined the proteins changes in DDX31-depleted BCa cells with shot-gun proteome and bioinformatic analyses. RESULTS We found that DDX31 was significantly upregulated in 7 of 9 BCa cell lines, which possess p53 mutations. Immunohistochemical analysis revealed that DDX31 expression (score ≥4) was associated with a significantly worse cancer-disease specific survival (HR 3.565, p = 0.041) than those with low DDX31 protein expression (score ≤ 3 ; log-rank, p = 0.007). Deletion of DDX31 expression by siRNA led to p53 stabilization, resulting in significant growth suppression in p53 wild type BCa (WT) cells, but not in p53 mutant (MT) cells. Notably, in MT cells, deletion of DDX31 expression led to the significant suppression of both migration and invasion abilities (wound-healing, p = 0.0038; invasion, p = 0.0016, respectively). Through the proteome and bioinformatics analyses, DDX31 might be involved in molecular pathways regulating morphological changes and cytoskeletal organization. CONCLUSIONS Overexpression of a novel nucleolar protein DDX31 is critically involved in advanced events such as cell migration and invasion of BCa. Together, we suggest that DDX31 may play the distinct important roles in proliferation ability and cytoskeletal organization depending on p53 mutation status. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e604 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Kei Daizumoto More articles by this author Tomoya Fukawa More articles by this author Hisanori Uehara More articles by this author Toyomasa Katagiri More articles by this author Hiro-omi Kanayama More articles by this author Expand All Advertisement Advertisement PDF DownloadLoading ...