Application of cancer therapy of senescence-associated microRNA

2016 Fiscal Year Final Research Report

• Project/Area Number: 26290047
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Tumor diagnostics
• Research Institution: Hiroshima University
• Principal Investigator: Tahara Hidetoshi 広島大学, 医歯薬保健学研究院, 教授 (00271065)
• Co-Investigator(Kenkyū-buntansha): 塩谷 文章 国立研究開発法人国立がん研究センター, その他部局等, 研究員 (10627665)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: PRPF19 / 老化 / がん / 膵がん

Outline of Final Research Achievements

This study aimed to reveal the tumor-suppressive mechanisms by PRPF19 siRNA. PRPF19 siRNA induced p53-dependent senescence-like cell cycle arrest in normal fibroblasts. However, DNA damage response kinases, ATR and ATM, are insufficient in p53 accumulation by PRPF19 siRNA in spite of accumulated DNA damage. On the other hand, PRPF19 siRNA induced mitotic cell death in cancer cells and pancreatic cancer cell lines are especially more sensitive to a low concentration of siRNA. Importantly, it is suggested that splicing deregulation by PRPF19 siRNA triggers tumor suppression because PRPF19 siRNA generated more intron-retaining products in cancer cells than normal cells. Moreover, PRPF19 siRNA suppressed tumor growth in a xenograft mouse model, indicating that PRPF19 is a potent molecular target for anti-cancer therapeutics.

Free Research Field

マイクロRNA、エクソソーム、がん、老化