Elucidation of epigenetic modification mechanisms of long non-coding RNAs

• 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(Kenkyū-buntansha): 西田 尚弘 大阪大学, 医学系研究科, 助教 (50588118) ; 今野 雅允 大阪大学, 医学系研究科, 寄附講座助教 (80618207) ; 川本 弘一 大阪大学, 医学系研究科, 特任助教(常勤) (30432470) ; 小関 準 大阪大学, 医学系研究科, 特任助教(常勤) (20616669)
• 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
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• 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.

Research Products

• [Journal Article] Impact of capecitabine and S-1 on anticoagulant activity of warfarin in patients with gastrointestinal cancer. (2016)
  • Author(s): Hata, T., Kudo, T., Sakai, D., Takahashi, H., Haraguchi, N., Nishimura, J., Hata, T., Mizushima, T., Yamamoto, H., Doki, Y., Mori, M., Satoh, T.
  • Journal Title: Cancer Chemother Pharmacol. Volume: 78 Issue: 2 Pages: 389-396
  • DOI: 10.1007/s00280-016-3080-0
  • Peer Reviewed / Open Access
• [Journal Article] Efficacy and Safety of Regorafenib or TAS-102 in Patients with Metastatic Colorectal Cancer Refractory to Standard Therapies. (2016)
  • Author(s): Sueda, T., Sakai, D., Kudo, T., Sugiura, T., Takahashi, H., Haraguchi, N., Nishimura, J., Hata, T., Hayashi, T., Mizushima, T., Doki, Y., Mori, M., Satoh, T.
  • Journal Title: Anticancer Res. Volume: 36 Pages: 4299-4306
  • Peer Reviewed / Open Access
• [Journal Article] Multi-center Clinical Study Group of Osaka, Colorectal Cancer Treatment Group (MCSGO). Combination antiemetic therapy with aprepitant/fosaprepitant in patients with colorectal cancer receiving oxaliplatin-based chemotherapy (SENRI trial): a multicentre, randomised, controlled phase 3 trial. (2015)
  • Author(s): Nishimura J, Satoh T, Fukunaga M, Takemoto H, Nakata K, Ide Y, Fukuzaki T, Kudo T, Miyake Y, Yasui M, Morita S, Sakai D, Uemura M, et al.
  • Journal Title: Eur J Cancer Volume: 51(10) Issue: 10 Pages: 1274-82
  • DOI: 10.1016/j.ejca.2015.03.024
  • Peer Reviewed