Analysis of long non-coding RNAs that predict biological malignancy in GIST

• Project/Area Number: 25670371
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Gastroenterology
• Research Institution: Sapporo Medical University
• Principal Investigator: SHINOMURA Yasuhisa 札幌医科大学, 医学部, 教授 (90162619)
• Co-Investigator(Kenkyū-buntansha): NOSHO Katsuhiko 札幌医科大学, 医学部, 講師 (10597339)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: GIST / ゲノム / HOTAIR / non-coding RNA / 次世代シークエンサー / ncRNA / ChIP-seq

Outline of Final Research Achievements

Large intergenic noncoding RNAs (lincRNA) have been less studied than miRNAs in cancer, although both offer considerable theranostic potential. In this study, we identified frequent upregulation of miR-196a and lincRNA HOTAIR in high-risk gastrointestinal stromal tumors (GIST). miR-196a genes are located within the HOX gene clusters and microarray expression analysis revealed that the HOXC and HOTAIR gene were also coordinately upregulated in GISTs which overexpress miR-196a. In like manner, overexpression of HOTAIR was also strongly associated with high-risk grade and metastasis among GIST specimens. RNA interference-mediated knockdown of HOTAIR altered the expression of reported HOTAIR target genes and suppressed GIST cell invasiveness. These findings reveal concurrent overexpression of HOX genes with noncoding RNAs in human cancer in this setting, revealing miR-196a and HOTAIR as potentially useful biomarkers and therapeutic targets in malignant GISTs.

Research Products

• [Journal Article] Association of microRNA-31-5p with clinical efficacy of anti-EGFR therapy in patients with metastatic colorectal cancer (2015)
  • Author(s): Igarashi H, Kurihara H, Mitsuhashi K, Ito M, Okuda H, Kanno S, Naito T, Yoshii S, Takahashi H, Kusumi T, Hasegawa T, Sukawa Y, Adachi Y, Okita K, Hirata K, Imamura Y, Baba Y, Imai K, Suzuki H, Yamamoto H, Nosho K, Shinomura Y
  • Journal Title: Ann Surg Oncol Volume: 14 Issue: 8 Pages: 4264-4267
  • DOI: 10.1245/s10434-014-4264-7
  • Peer Reviewed / Open Access
• [Journal Article] An updated review of gastric cancer in the next-generation sequencing era : Insights from bench to bedside and vice versa (2014)
  • Author(s): Yamamoto H (他14名), Nosho K, Shinomura Y
  • Journal Title: World J Gastroenterol Volume: 20 Issue: 14 Pages: 3927-3937
  • DOI: 10.3748/wjg.v20.i14.3927
  • Peer Reviewed / Open Access
• [Journal Article] Association of microRNA-31 with BRAF mutation, colorectal cancer survival, and serrated pathway (2014)
  • Author(s): Nosho K (他18名), Igarashi H, Ito M, Nojima M, Yamamoto H, Shinomura Y
  • Journal Title: Carcinogenesis Volume: 35 Issue: 4 Pages: 776-783
  • DOI: 10.1093/carcin/bgt374
  • Peer Reviewed
• [Journal Article] Aberrant methylation of microRNA-34b/c is a predictive marker of metachronous gastric cancer risk (2013)
  • Author(s): Suzuki R, Nosho K (他14名), Yamamoto H, Shinomura Y
  • Journal Title: J Gastroenterol Volume: (Epub ahead of print) Issue: 7 Pages: 1135-1144
  • DOI: 10.1007/s00535-013-0861-7
  • Peer Reviewed / Open Access
• [Presentation] 消化管間質腫瘍におけるmicroRNA遺伝子のエピジェネティックな制御 (2014)
  • Author(s): 新沼猛, 篠村恭久, 鈴木拓
  • Organizer: 第73回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] 消化管間質腫瘍の再発に関するmicroRNAの解析 (2014)
  • Author(s): 伊早坂舞, 篠村恭久, 鈴木拓
  • Organizer: 第73回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] 消化器癌の分子標的治療の現状と課題 (2013)
  • Author(s): 篠村 恭久
  • Organizer: 第21回日本消化器病関連学会集会
  • Place of Presentation: 東京国際フォーラム（東京都千代田区）
• [Presentation] マイクロRNA遺伝子のエピジェネティクス異常と臨床応用 (2013)
  • Author(s): 鈴木 拓
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）