Molecular function of repetitive RNA which accerelates pancreatic carcinogenesis

• Project/Area Number: 26860492
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Gastroenterology
• Research Institution: The University of Tokyo
• Principal Investigator: Kishikawa Takahiro 東京大学, 医学部附属病院, 特任臨床医 (00724171)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: ノンコーディングRNA / 膵がん / 膵癌 / 次世代シークエンス変異解析 / DNAダメージ修復機能の解析 / トランスジェニックマウスの作成 / DNAダメージ修復の解析 / 網羅的遺伝子解析

Outline of Final Research Achievements

We focus on repetitive RNAs which are aberrantly expressed in pancreatic cancer tissue and showed their biological significance during oncogenic process. Mouse repetitive RNAs start to be expressed from pre-cancer benign tumor. The rates of random mutation and malignant transformation are increased in repetitive RNA-overexpressing precancer cells due to impairment of DNA damage repair machinery. These results suggest that repetitive RNA functions as "intrinsic mutagen" and accerelates oncogenic process.

Research Products

• [Journal Article] Repression of miRNA function mediates inflammation-associated colon tumorigenesis. (2017)
  • Author(s): Yoshikawa T., J. F. Wu, M. Otsuka, T. Kishikawa, N. Suzuki, A. Takata, M. Ohno, R. Ishibashi, M. Yamagami, R. Nakagawa, N. Kato, M. Miyazawa, J. Han, and K. Koike
  • Journal Title: Gastroenterology Volume: 152 Issue: 3 Pages: 631-643
  • DOI: 10.1053/j.gastro.2016.10.043
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Satellite RNAs promote pancreatic oncogenic process via the dysfunction of YBX1. (2016)
  • Author(s): Kishikawa T, Otsuka M, Yoshikawa T, Ohno M, Ijichi H, and Koike K
  • Journal Title: Nature Communications Volume: 7 Issue: 1 Pages: 13006-13006
  • DOI: 10.1038/ncomms13006
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Quantitation of circulating satellite RNAs in pancreatic cancer patients. (2016)
  • Author(s): Kishikawa T, Otsuka M, Yoshikawa T, Ohno M, Yamamoto K, Yamamoto N, Kotani A, and Koike K
  • Journal Title: JCI Insight Volume: 1
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Mutual antagonism between hepatitis B viral mRNA and host microRNA let-7. (2016)
  • Author(s): Takata A, Otsuka M, Ohno M, Kishikawa T, Yoshikawa T, Koike K.
  • Journal Title: Sci Rep. Volume: 6 Issue: 1 Pages: 23237-23237
  • DOI: 10.1038/srep23237
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Circulating RNAs as new biomarkers for detecting pancreatic cancer (2015)
  • Author(s): Kishikawa, T. Otsuka, M. Ohno, M. Yoshikawa, T. Takata, A. Koike, K.
  • Journal Title: World J Gastroenterol Volume: 21(28) Issue: 28 Pages: 8527-8540
  • DOI: 10.3748/wjg.v21.i28.8527
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Decreased miR122 in hepatocellular carcinoma leads to chemoresistance with increased arginine (2015)
  • Author(s): Kishikawa, T. Otsuka, M. Tan, P. S. Ohno, M. Sun, X. Yoshikawa, T. Shibata, C. Takata, A. Kojima, K. Takehana, K. Ohishi, M. Ota, S. Noyama, T. Kondo, Y. Sato, M. Soga, T. Hoshida, Y. Koike, K.
  • Journal Title: Oncotarget Volume: 6 Pages: 8339-52
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] ROCK inhibition enhances microRNA function by promoting deadenylation of targeted mRNAs via increasing PAIP2 expression (2015)
  • Author(s): Yoshikawa, T. Wu, J. Otsuka, M. Kishikawa, T. Ohno, M. Shibata, C. Takata, A. Han, F. Kang, Y. J. Chen, C. A. Shyu, A. B. Han, J. Koike, K
  • Journal Title: Nucleic Acids Res Volume: 43(15) Issue: 15 Pages: 7577-89
  • DOI: 10.1093/nar/gkv728
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Development of a screening method to identify regulators of MICA shedding. (2015)
  • Author(s): Kishikawa T, Otsuka M, Ohno M, Yoshikawa T, Sato M, Koike K.
  • Journal Title: Biochem Biophys Res Commun. Volume: 465 Issue: 4 Pages: 764-768
  • DOI: 10.1016/j.bbrc.2015.08.081
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Diagnostic and therapeutic application of noncoding RNAs for hepatocellular carcinoma. (2015)
  • Author(s): Shibata C, Otsuka M, Kishikawa T, Ohno M, Yoshikawa T, Takata A, Koike K.
  • Journal Title: World J Hepatol. Volume: 27 Issue: 1 Pages: 1-6
  • DOI: 10.4254/wjh.v7.i1.1
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Specific delivery of microRNA93 into HBV-replicating hepatocytes downregulates protein expression of liver cancer susceptible gene MICA (2014)
  • Author(s): Ohno M, Otsuka M, Kishikawa T, Shibata C, Yoshikawa T, Takata A, Muroyama R, Kowatari N, Sato M, Kato N, Kuroda S, Koike K
  • Journal Title: Oncotarget Volume: 30 Pages: 5581-90
  • Peer Reviewed / Open Access
• [Journal Article] The role of microRNAs in hepatocarcinogenesis: current knowledge and future prospects. (2014)
  • Author(s): Otsuka M, Kishikawa T, Yoshikawa T, Ohno M, Takata A, Shibata C, Koike K.
  • Journal Title: J Gastroenterol. Volume: 49 Issue: 2 Pages: 173-84
  • DOI: 10.1007/s00535-013-0909-8
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] 膵がんの早期発見を可能にする血清中の反復配列RNAの高感度検出法の開発 (2017)
  • Author(s): 岸川孝弘 大塚基之 大野元子 山上まり 石橋嶺 關場一磨 鈴木辰典 小池和彦
  • Organizer: 第54回日本臨床分子医学会学術総会
  • Place of Presentation: 東京国際フォーラム(東京)
  • Year and Date: 2017-04-14
• [Presentation] High sensitive detecting procedure of circulating repetitive RNA as a novel early marker of pancreatic cancer. (2017)
  • Author(s): Kishikawa T. Otsuka M. Ohono M. Yamagami M. Ishibashi R. Sekiba K. Suzuki T. Koike K
  • Organizer: AACR annual meeting 2017
  • Place of Presentation: Washinton DC(USA)
  • Year and Date: 2017-04-02
  • Int'l Joint Research
• [Presentation] 反復配列RNAの異常発現が膵発癌を促進する分子生物学的機構の解明 (2016)
  • Author(s): 岸川孝弘 大塚基之 吉川剛史 大野元子 伊地知秀明 小池和彦
  • Organizer: G-plus
  • Place of Presentation: ホテルイースト東京21Aホール(東京)
  • Year and Date: 2016-12-17
• [Presentation] Deregulated transcription of mouse satellite sequences accelerates oncogenic processes via functional inhibition of YBX1 protein (2016)
  • Author(s): Kishikawa T. Otsuka M. Yoshikawa T. Ohono M. Koike K
  • Organizer: AACR annual meeting 2016
  • Place of Presentation: New Orleans(USA)
  • Year and Date: 2016-04-19
  • Int'l Joint Research
• [Presentation] Deregulated transcription of mouse satellite sequences accelerates oncogenic processes via functional inhibition of YBX1 protein (2016)
  • Author(s): Kishikawa, T. Otsuka, M. Ohno, M. Yoshikawa, T. Koike, K.
  • Organizer: AACR annual meeting 2016
  • Place of Presentation: New Orleans
  • Year and Date: 2016-04-17
  • Int'l Joint Research
• [Presentation] 酸化ストレスを介した膵発癌プロセスを加速させるノンコーディングサテライトRNAの異常発現 (2015)
  • Author(s): 岸川孝弘 大塚基之 小池和彦
  • Organizer: 第101回 日本消化器病学会総会
  • Place of Presentation: 仙台
  • Year and Date: 2015-04-22
• [Presentation] Alternation in microRNA expression profile in the process of pancreatic carcinogenesis (2015)
  • Author(s): Kishikawa, T. Otsuka, M. Ohno, M. Yoshikawa, T. Koike, K.
  • Organizer: AACR annual meeting 2015
  • Place of Presentation: Phiradelphia
  • Year and Date: 2015-04-18
  • Int'l Joint Research
• [Presentation] Detection of human satellite RNA in the serum of high-risk patients of pancreatic cancer (2014)
  • Author(s): Takahiro Kishikawa, Motoyuki Otsuka, Takeshi Yoshikawa, Motoko Ohno, Kazuhiko Koike
  • Organizer: AACR annual meeting 2014
  • Place of Presentation: San Diego
  • Year and Date: 2014-04-06