MP58-10 IFIT5 PROMOTES EMT VIA DOWN-REGULATION OF MATURE MIR-99A IN BLADDER CANCER

Abstract

You have accessJournal of UrologyBladder Cancer: Basic Research & Pathophysiology II1 Apr 2018MP58-10 IFIT5 PROMOTES EMT VIA DOWN-REGULATION OF MATURE MIR-99A IN BLADDER CANCER Jun Huang, U-Ging Lo, Jer-Tsong Hsieh, Dalin He, and Kaijie Wu Jun HuangJun Huang More articles by this author , U-Ging LoU-Ging Lo More articles by this author , Jer-Tsong HsiehJer-Tsong Hsieh More articles by this author , Dalin HeDalin He More articles by this author , and Kaijie WuKaijie Wu More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.1842AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Relapse and progression of non-muscle invasive bladder cancer (BCa) after transurethral resection and intravesical Bacillus Calmette-Guerin (BCG) instillation remain major problems in BCa therapy. IFN-γ is increased after BCG treatment, and low dose of IFN-γ can increase BCa cell migration. It is known that IFN-γ can induce the expression of IFIT5 (interferon induced protein with tetratricopeptide repeats 5), however, the expression and function of IFIT5 in BCa are still unknown. METHODS Expression of IFIT5 in BCa tissues were investigated by immunohistochemical staining and database (TCGA and GEO) retrieving. Stable IFIT5 over-expression or knock-down BCa cell sublines were generated to investigate the role of IFIT5 on epithelial-mesenchymal transition (EMT), cell migration and invasion in vitro. MicroRNA PCR array and qRT-PCR were used to verify the specific microRNA regulated by IFIT5. Direct target of the specific microRNA was verified by dual luciferase reporter assay, and their relationship with IFIT5 was analyzed by western blot. Subcutaneous xenograft model was used to investigate the effects of IFIT5 on tumorigenesis and verify the in vitro data. RESULTS IFIT5 expression was higher in high-grade, carcinoma in situ (CIS)-positive or muscle-invasive BCa tissues, which predicted a poor survival of patients. Over-expression of IFIT5 in 5637 and 253J cells induced EMT, promoted cell migration and invasion, and decreased the expression of mature miR-99a, meanwhile knock-down of IFIT5 in UM-UC-3 and TCCSUP cells inhibited EMT, suppressed cell migration and invasion, and increased the expression of mature miR-99a. However, either over-expression or knock-down of IFIT5 had no effect on the expression of pre-miR-99a and pri-miR-99a. Furthermore, ICAM1 was shown as a direct target of miR-99a, and over-expression of miR-99a in IFIT5 over-expressing 5637 and 253J cells could reverse EMT, suppress cell migration and invasion, and decrease ICAM1 expression induced by IFIT5. In addition, overexpression of IFIT5 could enhance BCa tumorigenecity, and the expression of mature miR-99a was negatively regulated. CONCLUSIONS Interferon-induced gene IFIT5 may acts as an oncogene in BCa relapse and progression after BCG treatment, which induces EMT, promote cell migration and invasion, and increase the expression of ICAM1 via down-regulation of mature miR-99a. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e776 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Jun Huang More articles by this author U-Ging Lo More articles by this author Jer-Tsong Hsieh More articles by this author Dalin He More articles by this author Kaijie Wu More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...