The elucidation of biliary and pancreatic tumor's pathobiology through the functional analysis of novel Warburg effect-associated gene PTBP1

Research Project

Project/Area Number	16K10615
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Digestive surgery
Research Institution	Osaka Medical College
Principal Investigator	Asakuma Mitsuhiro 大阪医科大学, 医学部, 講師 (40559390)
Co-Investigator(Kenkyū-buntansha)	赤尾幸博岐阜大学, 大学院連合創薬医療情報研究科, 特任教授 (00222505) 廣川文鋭大阪医科大学, 医学部, 准教授 (20322373) 内山和久大阪医科大学, 医学部, 教授 (80232867)
Project Period (FY)	2016-04-01 – 2019-03-31
Project Status	Completed (Fiscal Year 2018)
Budget Amount *help	¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000) Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000) Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000) Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords	膵癌 / PTBP1 / ワールブルク効果 / スプライサー / ワールブルグ効果 / microRNA / ワーバーグ効果 / Warburg効果 / PTBP1遺伝子
Outline of Final Research Achievements	Previously, we indicated that the expression of PTBP1 was increased in colorectal tumor and gastric cancer. In this project, the expression of PTBP1 was increased in pancreatic cancer. Our findings suggest that PTBP1 is universal oncogene in various cancer. Knockdown of PTBP1 induced growth suppression in pancreatic cancer cells and this result suggest that PTBP1 has cancer promoted function. We performed mRNA sequence analysis in PTBP1-silencing pancreatic cancer cells and detected the PTBP1 associated genes. Also, the expression profiles of PTBP1 in normal tissues or fatal reaction of PTBP1 were revealed through the bioinformatics analysis.
Academic Significance and Societal Importance of the Research Achievements	PTBP1は普遍的がん遺伝子の可能性が示唆され、様々ながん種における病態解析や新規治療標的、バイオマーカーとして新規標的遺伝子となりうることが明らかとなった。また、PTBP1はがんエネルギー代謝に深く関連する遺伝子であり、PTBP1の機能解析を通じて、膵癌の病態が新たな観点か明らかになったと考えられる。