Regulation of nestin using microRNA: Examination for clinical application of pancreatic cancer therapy

• Project/Area Number: 25461027
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology (2015); Nippon Medical School (2013-2014)
• Principal Investigator: Ishiwata Toshiyuki 地方独立行政法人東京都健康長寿医療センター(東京都健康長寿医療センター研究所), 東京都健康長寿医療センター研究所, 研究部長 (90203041)
• Co-Investigator(Kenkyū-buntansha): MATSUDA YOKO 地方独立行政法人東京都健康長寿医療センター(東京都健康長寿医療センター研究所), 東京都健康長寿医療センター研究所, 研究員 (20363187) ; MATSUSHITA AKIRA 日本医科大学, 医学部, 助教 (70449263) ; SHINJI SEIICHI 日本医科大学, 医学部, 助教 (80409193)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 膵癌 / 癌幹細胞 / miRNA / スフェア形成能 / nestin / 分子標的治療 / Nestin / microRNA

Outline of Final Research Achievements

Pancreatic cancer is associated with extremely high mortality rates, therefore, there is an urgent need to develop new therapeutic options. Nestin is a member of class VI intermediate filament proteins, and is known as a pancreatic cancer stem cell marker. Nestin plays important roles in proliferation, invasion and metastasis of pancreatic cancer cells. In the present study, we tried to identify the microRNAs (miRNAs) which are correlated with stemness of pancreatic cancer. Among 1190 miRNAs, we identified 8 types of miRNA that decrease the number of spheres, and 1 miRNA (miR-4254) that increases the number of spheres. Transfection of miR-4254-expression vector to PANC-1 cells increased nestin and nanog mRNA levels in the cells. These findings suggest that miR-4254 takes part in regulation of the stemness of pancreatic cancer.

Research Products

• [Journal Article] Ａｄｍｉｎｉｓｔｒａｔｉｏｎ ｏｆ ｓｍａｌｌ ｉｎｔｅｒｆｅｒｉｎｇ ＲＮＡ ｔａｒｇｅｔｉｎｇ ｈｕｍａｎ ｎｅｓｔｉｎ ｉｎｈｉｂｉｔｓ ｐａｎｃｒｅａｔｉｃ ｃａｎｃｅｒ ｃｅｌｌ ｐｒｏｌｉｆｅｒａｔｉｏｎ ａｎｄ ｍｅｔａｓｔａｓｉｓ． (2016)
  • Author(s): Ｍａｔｓｕｄａ Ｙ, Ishiwata T, Yoshimura H, Yamashita S, Ushijima T, Arai T.
  • Journal Title: Ｐａｎｃｒｅａｓ Volume: ４５ Issue: 1 Pages: 93-100
  • DOI: 10.1097/mpa.0000000000000427
  • 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] Nestin delineates pancreatic cancer stem cells in metastatic foci of NOD/Shi-scid IL2Rγ(null) (NOG) mice (2014)
  • Author(s): Matsuda Y, Yoshimura H, Ueda J, Naito Z, Korc M and Ishiwata T
  • Journal Title: Ａｍｅｒｉｃａｎ Ｊｏｕｒｎａｌ ｏｆ Ｐａｔｈｏｌｏｇｙ Volume: 184 Pages: 674-85
  • Peer Reviewed
• [Journal Article] Phosphorylation of Thr(1495) of nestin in a mouse model of cerebral ischemia and reperfusion damage (2013)
  • Author(s): Matsuda Y, Suzuki G, Kusano T, Kawamoto Y, Yoshimura H, Fuse A, Yokota H, Naito Zand Ishiwata T
  • Journal Title: Ｐａｔｈｏｌｏｇｙ Ｉｎｔｅｒｎａｔｉｏｎａｌ Volume: 63 Issue: 9 Pages: 448-56
  • DOI: 10.1111/pin.12092
  • Peer Reviewed
• [Presentation] 癌幹細胞と上皮間葉転換を標的とした革新的な癌治療法 (2015)
  • Author(s): 石渡 俊行
  • Organizer: 第６１回日本病理学会秋期特別総会
  • Place of Presentation: 東京大学安田講堂（東京都文京区）
  • Year and Date: 2015-11-05
• [Remarks] 東京都健康長寿医療センター研究所 研究チーム紹介 高齢者がん研究
  • URL: http://www.tmghig.jp/J_TMIG/kenkyu/team/koureishagan.html