Basic study of a long non-coding RNA, H19, as a novel therapeutic target for pancreatic cancer

• Project/Area Number: 26870622
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Tumor biology; Digestive surgery
• Research Institution: Nippon Veterinary and Life Science University
• Principal Investigator: Yoshimura Hisashi 日本獣医生命科学大学, 獣医学部, 助教 (70645241)
• Research Collaborator: ISHIWATA Toshiyuki ; MATSUDA Yoko ; TAKAHASHI Kimimasa ; MICHISHITA Masaki ; YAMAMOTO Masami
• 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: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: H19 / long non-coding RNA / pancreatic cancer / 長鎖非コードRNA / 膵癌 / non-coding RNA

Outline of Final Research Achievements

Previously, we established a novel cell line derived from lung metastatic nodules developing after injection of PANC-1 human pancreatic carcinoma cells into an immunodeficient mouse. A microarray analysis showed that enhanced expression of H19 in lung metastasis derived cells compared to parental cells. In situ hybridization showed that H19 was detected in 17% of invasive ductal carcinomas and that H19 expression positively correlated with higher histological grades. Overexpression of H19 in PANC-1 cells induced higher motility and sphere formation ability whereas H19 inhibition using RNA interference technique showed opposite results. Intravenous injection of H19 knockdown PANC-1 cells yielded marked suppression of metastasis in immunodeficient mice. These findings suggest that H19 plays an important role in pancreatic cancer metastasis and H19 is a novel therapeutic target for metastasis of pancreatic cancer.

Research Products

• [Journal Article] Multispectral Imaging of Pancreatic Mixed Acinar-neuroendocrine-ductal Carcinoma with Triple-immunoenzyme Staining (2015)
  • Author(s): Yoshimura H, Matsuda Y, Matsushita A, Nakamura Y, Uchida E, Ishiwata T.
  • Journal Title: Journal of Nippon Medical School Volume: 82 Issue: 3 Pages: 122-123
  • DOI: 10.1272/jnms.82.122
  • NAID: 130005085396
  • ISSN: 1345-4676, 1347-3409
  • Peer Reviewed
• [Journal Article] Neuroendocrine carcinoma of the mammary gland in a dog. (2015)
  • Author(s): Nakahira R, Michishita M, Yoshimura H, Hatakeyama H, Takahashi K.
  • Journal Title: J Comp Pathol Volume: 152 Issue: 2-3 Pages: 188-191
  • DOI: 10.1016/j.jcpa.2014.12.009
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Inhibition of nestin suppresses stem cell phenotype of glioblastomas through the alteration of post-translational modification of heat shock protein HSPA8/HSC71 (2015)
  • Author(s): Matsuda Y, Ishiwata T, Yoshimura H, Hagio M, Arai T.
  • Journal Title: Cancer Letters Volume: 357(2) Issue: 2 Pages: 602-611
  • DOI: 10.1016/j.canlet.2014.12.030
  • Peer Reviewed
• [Journal Article] Cellular Sources of Tenascin-C in Canine Mammary Carcinomas (2014)
  • Author(s): Yosnimura H, Micnisnita M, Ohkusu-Tsukada K, Matsuda Y, Ishiwata T, Naito Z, Takahashi K.
  • Journal Title: Veterinary Pathology Volume: Published online first Issue: 1 Pages: 92-96
  • DOI: 10.1177/0300985814522817
  • Peer Reviewed / Open Access
• [Journal Article] Differences in indicators of malignancy between luminal epithelial cell type and myoepithelial cell type of simple solid carcinoma in the canine mammary gland. (2014)
  • Author(s): Yoshimura H, Nakahira R, Kishimoto TE, Michishita M, Ohkusu-Tsukada K, Takahashi K.
  • Journal Title: Vet Pathol Volume: 51 Issue: 6 Pages: 1090-1095
  • DOI: 10.1177/0300985813516637
  • Peer Reviewed
• [Journal Article] Inhibition of fibroblast growth factor receptor 2 attenuates proliferation and invasion of pancreatic cancer. (2014)
  • Author(s): Matsuda Y, Yoshimura H, Suzuki T, Uchida E, Naito Z, Ishiwata T.
  • Journal Title: Cancer Science Volume: 105 Issue: 9 Pages: 1212-1219
  • DOI: 10.1111/cas.12470
  • Description: in press
  • Peer Reviewed / Open Access
• [Journal Article] Simultaneous Detection of Different RNAs Using a Novel Branched DNA <i>in situ</i> Hybridization Method (2014)
  • Author(s): Yoshimura H, Matsuda Y, Kawamoto Y, Naito Z, Ishiwata T.
  • Journal Title: Journal of Nippon Medical School Volume: 81 Issue: 2 Pages: 62-63
  • DOI: 10.1272/jnms.81.62
  • NAID: 130004147290
  • ISSN: 1345-4676, 1347-3409
  • Peer Reviewed
• [Presentation] Roles of long non-coding RNA in growth and metastasis of pancreatic cancer (2017)
  • Author(s): Ishiwata T, Yoshimura H, Matsuda Y, Ishikawa N, Takubo K, Arai T, Aida J.
  • Organizer: 第106回日本病理学会総会
  • Place of Presentation: 京王プラザホテル（東京都新宿区）
  • Year and Date: 2017-04-29
• [Presentation] A long non-coding RNA, H19, as a novel therapeutic target for pancreatic cancer metastasis (2017)
  • Author(s): Ishiwata T, Yoshimura H, Matsuda Y, Ishikawa N, Takubo K, Arai T, Aida J.
  • Organizer: American Association for Cancer Research Annual Meeting 2017
  • Place of Presentation: Washington, D.C., U.S.A.
  • Year and Date: 2017-04-04
  • Int'l Joint Research
• [Presentation] Long non-coding RNA, H19 as a novel therapeutic target for metastasis of pancreatic cancer (2016)
  • Author(s): Ishiwata T, Yoshimura H, Matsuda Y, Ishikawa N, Arai T, Takubo K, Aida J.
  • Organizer: 第75回日本癌学会学術集会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2016-10-06
• [Presentation] 膵癌における fibroblast growth factor receptor-4 の抑制効 果の検討 (2014)
  • Author(s): 石渡俊行、吉村久志、松田陽子、村瀬めぐみ、鈴木妙子、河本陽子、川原清子、石渡俊二、内藤善哉
  • Organizer: 第73回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2014-09-26
• [Presentation] 長鎖non-coding RNA H19の膵癌における発現と役割 (2014)
  • Author(s): 吉村久志、松田陽子、内藤善哉、石渡俊行
  • Organizer: 第157回日本獣医学会学術集会
  • Place of Presentation: 札幌
  • Year and Date: 2014-09-11
  • Invited
• [Presentation] 膵癌の遊走、転移に対する治療標的としての長鎖non-coding RNA H19 (2014)
  • Author(s): 吉村久志、松田陽子、村瀬めぐみ、鈴木妙子、河本陽子、川原清子、内藤善哉、石渡俊行
  • Organizer: 第45回日本膵臓学会大会
  • Place of Presentation: 北九州
  • Year and Date: 2014-07-11
• [Presentation] 長鎖non-coding RNA H19の浸潤性膵管癌における発現と役割の検討 (2014)
  • Author(s): 吉村久志、松田陽子、村瀬めぐみ、川原清子、河本陽子、鈴木妙子、内藤善哉、石渡俊行
  • Organizer: 第103回日本病理学会総会
  • Place of Presentation: 広島
  • Year and Date: 2014-04-26
• [Presentation] 膵癌細胞の転移におけるnestin発現の制御 (2014)
  • Author(s): 松田陽子、石渡俊行、吉村久志、山下聡、牛島俊和、田久保海誉、新井富生
  • Organizer: 第103回日本病理学会総会
  • Place of Presentation: 広島
  • Year and Date: 2014-04-25
• [Presentation] Long non-coding RNA H19 as a novel therapeutic target for pancreatic cancer (2014)
  • Author(s): Yoshimura H, Matsuda Y, Suzuki T, Naito Z, Ishiwata T.
  • Organizer: American association for cancer research, 105th annual meeting
  • Place of Presentation: San Diego, USA
  • Year and Date: 2014-04-09
• [Presentation] Inhibitory effects and regulatory mechanism of nestin in pancreatic cancer (2014)
  • Author(s): Matsuda Y, Ishiwata T, Yoshimura H, Yamashita S, Ushijima T, Takubo K, Arai T.
  • Organizer: American association for cancer research, 105th annual meeting
  • Place of Presentation: San Diego, USA
  • Year and Date: 2014-04-08