Anti-proliferative activity of Adenoviral vector expressing short hairpin RNA targeting G-Protein coupled receptor (GPR87) in urothelial carcinoma

2015 Fiscal Year Final Research Report

• Project/Area Number: 25462482
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Urology
• Research Institution: Kagawa University
• Principal Investigator: zhang xia 香川大学, 医学部, 助教 (30524061)
• Co-Investigator(Kenkyū-buntansha): Sugimoto Mikio 香川大学, 医学部, 准教授 (10243768) ; Kakehi Yoshiyuki 香川大学, 医学部, 教授 (20214273) ; Liu Dage 香川大学, 医学部, 助教 (30314941) ; Hayashita Yushi 香川大学, 医学部, 助教 (30615034) ; Hirama Hiromi 香川大学, 医学部, 助教 (50552725)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: GPR87 / shRNA / Adenovirus / Gene therapy

Outline of Final Research Achievements

GPR87 is a newly deorphanized member of the cell surface molecule G protein-coupled receptor family. GPR signaling was shown to play a role in promotion of cell growth and survival, metastasis, and drug resistance. To explore effective gene therapies for GPR87-expressing cancers including urothelial cancer, we constructed an adenoviral vector expressing short hairpin RNA targeting GPR87 (Ad-shGPR87). We found that Ad-shGPR87 effectively inhibited the proliferation of GPR87-expressing cell lines both in vitro and in vivo. With this effective tool, we then analyzed the intracellular pathways to uncover the mechanism by which GPR87 is able to regulate the proliferation and survival of human bladder cancer cells. Further, knockdown of GPR87 led to a p53-dependent signal transduction and caused apoptosis in the bladder cancer cells. Consequently, GPR87 appeared to be a promising target for gene therapy. These results of were adopted by domestic and international conferences.

Free Research Field

医歯薬学