Pathogenesis induced by interaction between microRNA and HBV transcripts

• Project/Area Number: 16K09344
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: The University of Tokyo
• Principal Investigator: KONDO Yuuji 東京大学, 医学部附属病院, 登録診療員 (00572231)
• Co-Investigator(Kenkyū-buntansha): 大塚 基之 東京大学, 医学部附属病院, 講師 (90518945)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: HBV / microRNA / decoy / 核酸 / ウイルス / Ｂ型肝炎 / おとり / ウィルス

Outline of Final Research Achievements

To better understand the pathological roles of HBV RNAs, the sequence homologies between HBVRNA and host microRNAs were examined. Pre S sequences in the HBVRNA have similarities to the let7g sequences and indeed preS2 RNA suppressed thelet7g function. Because let7 is a representative tumor-suppressive microRNA, this may explain the increased probabilities of HCC during HBV infection. On the other hand, let7 suppressed HBV cccDNA production. Therefore, the interaction between virus and host RNA factors may play roles in the viral pathogenesis.

Academic Significance and Societal Importance of the Research Achievements

B型肝炎ウイルスの病態生理形成にウイルスRNAが関与している可能性を検討した。その結果、B型肝炎ウイルス由来のRNAの一部が、宿主のmicroRNA let7と配列が近似し、その結果、let7を吸着して、その本来の機能を阻害していることを見出した。Let7はがん抑制性のmicroRNAのひとつなので、この作用が、HBV感染での易発癌性に関与していることが示唆されるいっぽう、let7はHBVRNAに作用してウイルスの持続感染に重要なcccDNAの産生を阻害した。ウイルスと宿主の分子的なせめぎあいの解明は病態を明らかにするうえで重要なことが示された。

Research Products

• [Journal Article] Inhibition of HBV Transcription From cccDNA With Nitazoxanide by Targeting the HBx?DDB1 Interaction (2019)
  • Author(s): Sekiba Kazuma、Otsuka Motoyuki、Ohno Motoko、Yamagami Mari、Kishikawa Takahiro、Suzuki Tatsunori、Ishibashi Rei、Seimiya Takahiro、Tanaka Eri、Koike Kazuhiko
  • Journal Title: Cellular and Molecular Gastroenterology and Hepatology Volume: 7 Issue: 2 Pages: 297-312
  • DOI: 10.1016/j.jcmgh.2018.10.010
  • Peer Reviewed / Open Access
• [Journal Article] Inflammation and de-differentiation in pancreatic carcinogenesis (2018)
  • Author(s): Seimiya Takahiro、Otsuka Motoyuki、Iwata Takuma、Tanaka Eri、Suzuki Tatsunori、Sekiba Kazuma、Yamagami Mari、Ishibashi Rei、Koike Kazuhiko
  • Journal Title: World Journal of Clinical Cases Volume: 6 Issue: 15 Pages: 882-891
  • DOI: 10.12998/wjcc.v6.i15.882
  • Peer Reviewed / Open Access
• [Journal Article] Hepatitis B virus pathogenesis: Fresh insights into hepatitis B virus RNA (2018)
  • Author(s): Sekiba Kazuma、Otsuka Motoyuki、Ohno Motoko、Yamagami Mari、Kishikawa Takahiro、Suzuki Tatsunori、Ishibashi Rei、Seimiya Takahiro、Tanaka Eri、Koike Kazuhiko
  • Journal Title: World Journal of Gastroenterology Volume: 24 Issue: 21 Pages: 2261-2268
  • DOI: 10.3748/wjg.v24.i21.2261
  • Peer Reviewed / Open Access
• [Journal Article] Satellite RNA Increases DNA Damage and Accelerates Tumor Formation in Mouse Models of Pancreatic Cancer (2018)
  • Author(s): Kishikawa Takahiro、Otsuka Motoyuki、Suzuki Tatsunori、Seimiya Takahiro、Sekiba Kazuma、Ishibashi Rei、Tanaka Eri、Ohno Motoko、Yamagami Mari、Koike Kazuhiko
  • Journal Title: Molecular Cancer Research Volume: 16 Issue: 8 Pages: 1255-1262
  • DOI: 10.1158/1541-7786.mcr-18-0139
  • Peer Reviewed / Open Access
• [Journal Article] RASAL1 is a potent regulator of hepatic stellate cell activity and liver fibrosis (2017)
  • Author(s): Takata Akemi、Otsuka Motoyuki、Kishikawa Takahiro、Yamagami Mari、Ishibashi Rei、Sekiba Kazuma、Suzuki Tatsunori、Ohno Motoko、Yamashita Yui、Abe Takaya、Masuzaki Ryota、Ikenoue Tsuneo、Koike Kazuhiko
  • Journal Title: Oncotarget Volume: 8 Issue: 39 Pages: 64840-64852
  • DOI: 10.18632/oncotarget.17609
  • Peer Reviewed / Open Access
• [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] MicroRNAs and liver disease (2017)
  • Author(s): Otsuka M, Kishikawa T, Yoshikawa T, Yamagami M, Ohno M, Takata A, Shibata C, Ishibashi R, Koike K.
  • Journal Title: J Hum Genet. Volume: 62 Issue: 1 Pages: 75-80
  • DOI: 10.1038/jhg.2016.53
  • Peer Reviewed / Open Access / Acknowledgement Compliant