Elucidation of the role of microRNA as a cancer treatment-resistant mechanism by autophagy

• Project/Area Number: 26670607
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Digestive surgery
• Research Institution: Kyushu University
• Principal Investigator: NAKATA Kohei 九州大学, 大学病院, 特別教員 (30419569)
• Co-Investigator(Kenkyū-buntansha): MAEYAMA Ryo 九州大学, 医学研究院, 共同研究員 (10611668) ; NAGAI Eishi 九州大学, 医学研究院, 准教授 (30264021) ; EGAMI Takuya 九州大学, 医学研究院, 共同研究員 (40507787) ; MIYASAKA Yoshihiro 九州大学, 医学研究院, 助教 (40507795)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: オートファジー / マイクロRNA / 膵臓癌

Outline of Final Research Achievements

As the existing chemotherapy has little effect on cancer stem cells, which have remained in the stationary phase, mechanism elucidation of the cancer stem cells is expected. It was recently reported that autophagy is involved in the maintenance of blood stem cells, and we have been reporting the relationship between the micro-RNA and pancreatic cancer malignancy. From these, we study the involvement of cancer stem cells maintenance mechanism by autophagy and micro-RNA.
We established the evaluation method of autophagy and the stemness of pancreatic cancer cells. Further, we reported that micro RNA-373 suppressed the invasion of cancer cells, through the inhibition of the epithelial-mesenchymal transition. We also reported that overexpression of micro RNA-5100 reduced colony-forming, invasion, and migration ability of pancreatic cancer cells.

Research Products

• [Journal Article] Hypoxic stellate cells of pancreatic cancer stroma regulate extracellular matrix fiber organization and cancer cell motility. (2016)
  • Author(s): Sada M, Ohuchida K, Horioka K, Okumura T, Moriyama T, Miyasaka Y, Ohtsuka T, Mizumoto K, Oda Y, Nakamura M
  • Journal Title: Cancer letter Volume: 372 Pages: 1499-1508
  • DOI: 10.1016/j.canlet.2016.01.016
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Suppression of CD51 in pancreatic stellate cells inhibits tumor growth by reducing stroma and altering tumor-stromal interaction in pancreatic cancer. (2016)
  • Author(s): Horioka K, Ohuchida K, Sada M, Zheng B, Moriyama T, Fujita H, Manabe T, Ohtsuka T, Shimamoto M, Miyazaki T, Mizumoto K, Oda Y, Nakamura M.
  • Journal Title: International Journal of Oncology Volume: 48 Pages: 1499-1508
  • DOI: 10.3892/ijo.2016.3374
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Overexpression of microRNA-5100 decreases the aggressive phenotype of pancreatic cancer cells by targeting PODXL (2016)
  • Author(s): Chijiiwa Y, Moriyama T, Ohuchida K, Nabae T, Ohtsuka T, Miyasaka Y, Fujita H, Maeyama R, Manabe T, Abe A, Mizuuchi Y, Oda Y, Mizumoto K, Nakamura M
  • Journal Title: Int J Oncol. Volume: 48 Pages: 1499-1508
  • DOI: 10.3892/ijo.2016.3389
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] 膵癌におけるmiRNA発現と上皮間葉転換 (2015)
  • Author(s): 仲田興平、大内田研宙、大塚隆生、中村雅史
  • Journal Title: 胆と膵 Volume: 36 Pages: 1117-1122
• [Journal Article] MicroRNA-373 is down regulated in pancreatic cancer and inhibits cancer cell incasion (2014)
  • Author(s): Nakata K, Ohuchida K, Mizumoto K, Aishima S, Oda Y, Nagai E, Tanaka M
  • Journal Title: Annals of Surgical Oncology Volume: 21
  • DOI: 10.1245/s10434-014-3676-8
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] Pancreatic Stellate Cells Lead and Promote the Local Invasion of Cancer Cells, by Physically Remodeling the Extracellular Matrix with Collagen Fiber Alignment in Pancreatic Cancer (2015)
  • Author(s): Koikawa K, Ohuchida K, Sada M, Abe T, Endo S, Horioka K, Moriyama T, Miyasaka Y, Ohtsuka T, Ohuchida R, Ueki T, Nagai E, Mizumoto K, Nakamura M
  • Organizer: American Pancreatic Association 46th Annual Meeting
  • Place of Presentation: San Diego (USA)
  • Year and Date: 2015-11-04
  • Int'l Joint Research
• [Presentation] Suppression of CD51 in Pancreatic Stellate Cells Inhibits Tumor Growth by Reducing Stroma and Altering Tumor-Stromal Interaction in Pancreatic Cancer (2015)
  • Author(s): Horioka K, Ohuchida K, Sada M, Zheng B, Ohtsuka T, Ueki T, Nagai E, Mizumoto K, Oda Y, Nakamura M
  • Organizer: American Pancreatic Association 46th Annual Meeting
  • Place of Presentation: San Diego (USA)
  • Year and Date: 2015-11-04
  • Int'l Joint Research
• [Presentation] オートファジーが膵癌の癌間質相互作用に与える影響の検討 (2015)
  • Author(s): 遠藤翔、仲田興平、大内田研宙、阿部俊也、肥川和寛、堀岡宏平、水内祐介、小田義直、水元一博、田中雅夫
  • Organizer: 第46回日本膵臓学会大会
  • Place of Presentation: 名古屋市
  • Year and Date: 2015-06-19
• [Presentation] 膵癌肝転移に関わるmicroRNAの検討 (2015)
  • Author(s): 千々岩芳朗、大内田研宙、水元一博、田中雅夫
  • Organizer: 第115回日本外科学会定期学術集会
  • Place of Presentation: 名古屋市
  • Year and Date: 2015-04-16
• [Presentation] 膵癌の肝転移におけるfollistatin-like1の役割 (2014)
  • Author(s): 堀岡宏平、大内田研宙、江口大樹、佐田政史、田中友晴、赤川進、藤原謙次、鄭彪、仲田興平、宮坂義浩、前山良、大塚隆生、水元一博、田中雅夫
  • Organizer: 第114回日本外科学会定期学術集会
  • Place of Presentation: 京都市
  • Year and Date: 2014-04-04
• [Presentation] 膵癌におけるTM4SF1発現の意義 (2014)
  • Author(s): 鄭彪、崔林、大内田研宙、進藤幸治、藤原謙次、赤川進、堀岡宏平、田中友晴、佐田政史、吉田真樹、千々岩芳朗、奥村隆志、仲田興平、大塚隆生、小田義直、水元一博、田中雅夫
  • Organizer: 第114回日本外科学会定期学術集会
  • Place of Presentation: 京都市
  • Year and Date: 2014-04-04