Elucidation of epigenetic modification mechanisms of long non-coding RNAs

2016 Fiscal Year Final Research Report

• Project/Area Number: 15K15475
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: General surgery
• Research Institution: Osaka University
• Principal Investigator: Kudo Toshihiro 大阪大学, 医学系研究科, 寄附講座助教 (20593859)
• Co-Investigator(Renkei-kenkyūsha): Ishii Hideshi 大阪大学, 大学院医学系研究科, 特任教授(常勤) (10280736) ; Mori Masaki 大阪大学, 大学院医学系研究科, 教授 (70190999)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Keywords: 癌 / 核酸 / 臨床

Outline of Final Research Achievements

Chemical modifications on long non-coding RNA (lncRNA) molecules potentially alter their biological functions. In this study, we have demonstrated functional alterations of lncRNAs upon induction of chemical modifications, such as methylations and acetylations. We have started with a comprehensive profiling of hypoxia-induced long lncRNAs, which could be good candidates for key oncogenic molecules in cancer microenvironment. By using PCR-based microarray method, we identified several candidate lncRNAs. In vitro functional assays revealed these lncRNAs could play an important role in cancer progression. Knockdown of RNA methylation enzyme reduced methylation levels of lncRNA transcripts and lead to functional alterations including growth inhibition, resistance to chemotherapeutic agents. These findings suggest that chemical modifications on lncRNAs is crucially involved in cancer progression and that the methylation enzyme could be a crucial therapeutic target.

Free Research Field

消化器癌化学療法