Research on molecular pathways of local invasion and distant metastasis based on pancreatic cancer - functional RNA expression analysis

• Project/Area Number: 18K16322
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Kagoshima University
• Principal Investigator: Idichi Tetsuya 鹿児島大学, 鹿児島大学病院, 医員 (70791531)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: マイクロRNA / 膵癌 / 機能性RNAネットワーク / Oncogene / tumor-suppressor / 機能性RANネットワーク

Outline of Final Research Achievements

Using the microRNA expression profile in pancreatic ductal adenocarcinoma(PDAC), it was demonstrated that miR-204, miR-130b, miR-30a, and miR-30c function as PDAC-suppressing microRNA, and are particularly involved in the metastasis and invasion of PDAC. RACGAP1, EPS8, ITGA2 / B1 and TOP2A were found as new target genes, and their functional analysis was performed as pancreatic cancer genes. Furthermore, we demonstrated that these genes are associated with PDAC prognosis and play an important role in the functional molecular network of PDAC.

Academic Significance and Societal Importance of the Research Achievements

膵癌における明確な有効性を持った治療標的分子は未だ同定できておらず、本研究における「癌抑制型マイクロRNA」を介した機能性RNAネットワークの探索は、今後の膵癌分子標的治療における重要な情報提供を期待できる。有効な治療法の少ない膵癌において、新規の膵癌転移・浸潤抑制型マイクロRNAを解析することで、膵癌予後に 関連するターゲット遺伝子を発見し、未だ報告のない新規分子やそれらの制御する機能性RNAネットワークの探求を行うことが可能だった。

Research Products

• [Journal Article] Role of miR-30a-3p Regulation of Oncogenic Targets in Pancreatic Ductal Adenocarcinoma Pathogenesis (2020)
  • Author(s): Shimomura H, Okada R, Tanaka T, Hozaka Y, Wada M, Moriya S, Idichi T, Kita Y, Kurahara H, Ohtsuka T, Seki N.
  • Journal Title: Int J Mol Sci Volume: 18 Issue: 18 Pages: 6459-6459
  • DOI: 10.3390/ijms21186459
  • Peer Reviewed / Open Access
• [Journal Article] Molecular Pathogenesis of Pancreatic Ductal Adenocarcinoma: Impact of miR-30c-5p and miR-30c-2-3p Regulation on Oncogenic Genes. (2020)
  • Author(s): Tanaka T, Okada R, Hozaka Y, Wada M, Moriya S, Satake S, Idichi T, Kurahara H, Ohtsuka T, Seki N.
  • Journal Title: Cancers Volume: 12 Issue: 10 Pages: 2731-2731
  • DOI: 10.3390/cancers12102731
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Gene Regulation by Antitumor miR-204-5p in Pancreatic Ductal Adenocarcinoma: The Clinical Significance of Direct RACGAP1 Regulation. (2019)
  • Author(s): Khalid M, Idichi T, Seki N, Wada M, Yamada Y, Fukuhisa H, Toda H, Kita Y, Kawasaki Y, Tanoue K, Kurahara H, Mataki Y, Maemura K, Natsugoe S.
  • Journal Title: Cancers (Basel) Volume: 11 Issue: 3 Pages: 327-327
  • DOI: 10.3390/cancers11030327
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Gene regulation by antitumor miR-130b-5p in pancreatic ductal adenocarcinoma: the clinical significance of oncogenic EPS8. (2019)
  • Author(s): Fukuhisa H, Seki N, Idichi T, Kurahara H, Yamada Y, Toda H, Kita Y, Kawasaki Y, Tanoue K, Mataki Y, Maemura K, Natsugoe S.
  • Journal Title: J Hum Genet. Volume: - Issue: 6 Pages: 521-534
  • DOI: 10.1038/s10038-019-0584-6
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] RNA‐sequence‐based microRNA expression signature in breast cancer: tumor‐suppressive miR‐101‐5p regulates molecular pathogenesis (2019)
  • Author(s): Toda Hiroko、Seki Naohiko、Kurozumi Sasagu、Shinden Yoshiaki、Yamada Yasutaka、Nohata Nijiro、Moriya Shogo、Idichi Tetsuya、Maemura Kosei、Fujii Takaaki、Horiguchi Jun、Kijima Yuko、Natsugoe Shoji
  • Journal Title: Molecular Oncology Volume: 14 Issue: 2 Pages: 426-446
  • DOI: 10.1002/1878-0261.12602
  • Peer Reviewed / Open Access
• [Journal Article] Molecular pathogenesis of esophageal squamous cell carcinoma: Identification of the antitumor effects of miR 145 3p on gene regulation. (2019)
  • Author(s): Shimonosono M, Idichi T, Seki N, Yamada Y, Arai T, Arigami T, Sasaki K, Omoto I, Uchikado Y, Kita Y, Kurahara H, Maemura K, Natsugoe S.
  • Journal Title: Int J Oncol. Volume: 54 Pages: 673-688
  • DOI: 10.3892/ijo.2018.4657
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Molecular pathogenesis of pancreatic ductal adenocarcinoma: Impact of passenger strand of pre-miR-148a on gene regulation. (2018)
  • Author(s): Idichi T, Seki N, Kurahara H, Fukuhisa H, Toda H, Shimonosono M, Okato A, Arai T, Kita Y, Mataki Y, Kijima Y, Maemura K, Natsugoe S.
  • Journal Title: Cancer Sci. Volume: 109 Issue: 6 Pages: 2013-2026
  • DOI: 10.1111/cas.13610
  • Peer Reviewed / Open Access
• [Journal Article] Involvement of anti-tumor miR-124-3p and its targets in the pathogenesis of pancreatic ductal adenocarcinoma: direct regulation of ITGA3 and ITGB1 by miR-124-3p. (2018)
  • Author(s): Idichi T, Seki N, Kurahara H, Fukuhisa H, Toda H, Shimonosono M, Yamada Y, Arai T, Kita Y, Kijima Y, Mataki Y, Maemura K, Natsugoe S.
  • Journal Title: Oncotarget Volume: 9(48) Issue: 48 Pages: 28849-28865
  • DOI: 10.18632/oncotarget.25599
  • Peer Reviewed / Open Access
• [Journal Article] Molecular pathogenesis of triple-negative breast cancer based on microRNA expression signatures: antitumor miR-204-5p targets AP1S3. (2018)
  • Author(s): Toda H, Kurozumi S, Kijima Y, Idichi T, Shinden Y, Yamada Y, Arai T, Maemura K, Fujii T, Horiguchi J, Natsugoe S, Seki N.
  • Journal Title: J Hum Genet Volume: 63(12) Issue: 12 Pages: 1197-1210
  • DOI: 10.1038/s10038-018-0510-3
  • Peer Reviewed
• [Presentation] The effect of microRNA-124 on the phosphorylation pathway of integrin. (2019)
  • Author(s): Tetsuya Idichi, Hiroshi Kurahara, Kousei Maemura, Yuko Mataki, Haruhi Fukuhisa, Yota Kawasaki, Satoru Iino, Masahiko Sakoda, Tanoue kiyonori, Shinichi Ueno, Hiroyuki Shinchi, Shouji Natsugoe
  • Organizer: 第31回日本肝胆膵外科学会学術集会
• [Presentation] インテグリンを介したmiR-124による膵癌リン酸化シグナルの制御機構 (2019)
  • Author(s): 伊地知徹也、蔵原弘、前村公成、又木雄弘、迫田雅彦、飯野聡、川崎洋太、田上聖徳、上野真一、新地洋之、夏越祥次
  • Organizer: 第74回日本消化器外科学会総会
• [Presentation] Invasion effect of Integrin α3/β1 (ITGA3/ITGB1) on pancreatic ductal adenocarcinoma (2019)
  • Author(s): Tetsuya Idichi, Hiroshi Kurahara, Kousei Maemura, Yuko Mataki, Yota Kawasaki, Satoru Iino, Masahiko Sakoda, Shinichi Ueno, Hiroyuki Shinchi, Shouji Natsugoe
  • Organizer: 第28回日本がん転移学会学術集会
• [Presentation] 膵癌における抑制型microRNA；passenger-strandを用いた機能性RNAネットワークの探索 (2019)
  • Author(s): 伊地知徹也、蔵原弘、前村公成、又木雄弘、飯野聡、川崎洋太、田上聖徳、下村寛貴、上野真一、新地洋之、夏越祥次
  • Organizer: 第30回日本消化器癌発生学会学術集会
• [Presentation] Exploring downstream gene signals using pancreatic cancer-suppressing microRNA (2018)
  • Author(s): Tetsuya Idichi、Hiroshi Kurahara、Kousei Maemura、Yuko Mataki、Yota Kawasaki、Satoru Iino、Masahiko Sakoda、Shinichi Ueno、Hiroyuki Shinchi、Shouji Natsugoe
  • Organizer: 第30回日本肝胆膵外科学会
• [Presentation] Suppressor effect of pancreatic adenocarcinoma in passenger strands of microRNA (2018)
  • Author(s): Tetsuya Idichi, Hiroshi Kurahara, Kosei Maemura, Yuko Mataki, Haruhi Fukuhisa, Masahiko Sakoda, Satoshi Iino, Yota Kawasaki, Hiroyuki Shinchi, Shinichi Ueno, Shoji Natsugoe
  • Organizer: 第77回日本癌学会学術総会