RNA editing in non-small cell lung cancer

• Project/Area Number: 15K20917
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Tumor diagnostics; Laboratory medicine
• Research Institution: The University of Tokyo
• Principal Investigator: Watanabe Kousuke 東京大学, 医学部附属病院, 助教 (50644291)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 肺がん / miRNA / RNA編集

Outline of Final Research Achievements

Genetic mutations play important roles in cancer development and progression, but RNA editing also alters RNA sequence and may contribute to cancer biology. The most prevalent form of RNA editing in human is Adenosine to Inosine editing (A to I editing) mediated by ADAR1 and ADAR2. Recent study has shown altered editing levels of protein coding genes in cancer, but RNA editing of miRNAs have not been studied in detail. The purpose of the study is to identify miRNAs that undergo A to I editing in non-small cell lung cancer (NSCLC).
Using the publicly available small RNA sequencing data of lung adenocarcinoma, we identified gain of editing in miR-200b and miR-381 and loss of editing in miR-99a, miR-379, miR-411, and miR-497. We analyzed the editing levels of miR-99a in 50 cases of surgically resected NSCLC, and loss of editing was observed in 19 cases. The loss of miR-99a editing was associated with relapse after surgery. The RNA editing of miR-99a can be used as a biomarker of NSCLC.

Research Products

• [Journal Article] High expression of IRE1 in lung adenocarcinoma is associated with a lower rate of recurrence. (2017)
  • Author(s): Sakatani T, Maemura K, Hiyama N, Amano Y, Watanabe K, Kage H, Fukayama M, Nakajima J, Yatomi Y, Nagase T, Takai D.
  • Journal Title: Jpn J Clin Oncol. Volume: 17 Issue: 6 Pages: 1-8
  • DOI: 10.1093/jjco/hyx031
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] The chimeric transcript RUNX1-GLRX5: a biomarker for good postoperative prognosis in Stage IA non-small-cell lung cancer (2016)
  • Author(s): Ishikawa R, Amano Y, Kawakami M, Sunohara M, Watanabe K, Kage H, Ohishi N, Yatomi Y, Nakajima J, Fukayama M, Nagase T, Takai D
  • Journal Title: Jpn J Clin Oncol Volume: 46 Pages: 185-9
  • DOI: 10.1093/jjco/hyv187
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Histone methylation-mediated silencing of miR-139 enhances invasion of non-small-cell lung cancer (2015)
  • Author(s): Kousuke Watanabe, Yosuke Amano, Rie Ishikawa, Mitsuhiro Sunohara, Hidenori Kage, Junji Ichinose, Atsushi Sano, Jun Nakajima, Masashi Fukayama, Yutaka Yatomi, Takahide Nagase, Nobuya Ohishi and Daiya Takai
  • Journal Title: Cancer Medicine Volume: 4 Issue: 10 Pages: 1573-82
  • DOI: 10.1002/cam4.505
  • Peer Reviewed / Open Access
• [Presentation] High expression of endoplasmic reticulum oxidoreductin (ERO) 1L is associated with resistance to cisplatin (2016)
  • Author(s): Toshio Sakatani, Keita Maemura, Noriko Hiyama, Yousuke Amano, Kousuke Watanabe, Hidenori Kage, Masashi Fukayama, Jun Nakajima, Yutaka Yatomi, Takahide Nagase, Daiya Takai
  • Organizer: Fourth AACR-IASLC International Joint Conference: Lung Cancer Translational Science from the Bench to the Clinic
  • Place of Presentation: San Diego, USA
  • Year and Date: 2016-01-04
  • Int'l Joint Research