The role of micro RNA in chemo- resistance of uterine serous carcinoma

• Project/Area Number: 24592498
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Yamagata University (2014); Tohoku University (2012-2013)
• Principal Investigator: NAGASE Satoru 山形大学, 医学部, 教授 (00292326)
• Co-Investigator(Kenkyū-buntansha): SUSUKI Fumihiko 東北大学, 医学(系)研究科(研究院), 助教 (20400343) ; YOSHINAGA Kousuke 東北大学, 医学(系)研究科(研究院), 非常勤講師 (40343058) ; TANNO Sumika 東北大学, 医学(系)研究科(研究院), 非常勤講師 (60509595)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2012: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
• Keywords: 子宮体癌 / 漿液性腺癌 / マイクロRNA / マイクロアレイ / 薬剤耐性

Outline of Final Research Achievements

To elucidate mechanisms of chemo-resistance for platinum and taxane from the aspect of microRNA (miRNA), we used USPC-1 and constructed its chemo-resistant variant PTX-R and CDDP-R. By microRNA microarray analysis, we focused on let-7c. We confirmed that the expression of let-7c was decreased significantly in both drug-resistant cells (P<0.05). Cell viability was decreased after let-7c mimic transfection to PTX-R followed by PTX treatment and similar transfection to CDDP-R followed by CDDP treatment. HMGA2 is known as the most famous target of let-7c and let-7c mimic transfection revealed decreased expression of HMGA2 (p<0.05). ABC transporters such as ABCB1, ABCC1, ABCC2, ABCG2, are the important molecules in the drug resistance, and the expression of ABCC1 was decreased significantly by let-7c inhibitor transfection to parental cells (p<0.05). These data shows that let-7c may involve in drug resistance of PTX and CDDP via HMGA2 or ABCC1 in USC.

Research Products

• [Journal Article] Inhibition of plasminogen activator inhibitor-1 is a potential therapeutic strategy in ovarian cancer. (2015)
  • Author(s): Mashiko S, Kitatani K, Toyoshima M, Ichimura A, Dan T, Usui T, Ishibashi M, Shigeta S, Nagase S, Miyata T, Yaegashi N
  • Journal Title: Cancer Biology & Therapy Volume: 16 Issue: 2 Pages: 253-260
  • DOI: 10.1080/15384047.2014.1001271
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] MicroRNA-101 targets EZH2, MCL-1 and FOS to suppress proliferation, invasion and stem cell-like phenotype of aggressive endometrial cancer cells. (2014)
  • Author(s): Konno Y, Dong P, Xiong Y, Suzuki F, Lu J, Cai M, Watari H, Mitamura T, Hosaka M, Hanley SJ, Kudo M, Sakuragi N.
  • Journal Title: Oncotarget Volume: 5(5) Pages: 6049-6062
  • NAID: 120005690901
• [Journal Article] Molecular Pathogenesis of Uterine Serous Carcinoma (2014)
  • Author(s): Satoru Nagase ・ Fumihiko Suzuki ・ Hideki Tokunaga ・Masafumi Toyoshima ・ Hiroki Utsunomiya ・Hitoshi Niikura ・ Nobuo Yaegashi
  • Journal Title: Curr Obstet Gynecol Rep Volume: 3 Issue: 1 Pages: 33-39
  • DOI: 10.1007/s13669-013-0069-0
  • Peer Reviewed
• [Journal Article] Decreased Expression of 14-3-3<i>σ</i> Is Predictive of Poor Prognosis for Patients with Human Uterine Papillary Serous Carcinoma (2013)
  • Author(s): 1. Suzuki F, Nagase S, Suzuki K, Oba E, Hiroki E, Matsuda Y, Akahira J, Nishigori H, Sugiyama T, Otsuki T, Yoshinaga K, Takano T, Niikura H, Ito K, Sasano H, and Yaegashi N
  • Journal Title: The Tohoku Journal of Experimental Medicine Volume: 231 Issue: 3 Pages: 193-199
  • DOI: 10.1620/tjem.231.193
  • NAID: 130004720755
  • ISSN: 0040-8727, 1349-3329
  • Peer Reviewed
• [Journal Article] MicroRNA-34b functions as a potential tumor suppressor in endometrial serous adenocarcinoma (2012)
  • Author(s): Hiroki E, Akahira J, et al
  • Journal Title: Int J Cancer Volume: (印刷中) Issue: 4 Pages: 395-404
  • DOI: 10.1002/ijc.27345
  • Peer Reviewed
• [Presentation] MiR-34b correlates tumor growth and invasion in uterine serous carcinoma. (2015)
  • Author(s): Fumihiko Suzuki, Satoru Nagase, Yoh Watanabe, Izumi Sato, Hiroki Utsunomiya, Michiko Kaiho, Hideki Tokunaga, Hitoshi Niikura, Tadao Takano, Hironobu Sasano and Nobuo Yaegashi
  • Organizer: 62nd Annual Meeting of the society for Reproductive Investigation
  • Place of Presentation: Hilton San Francisco （San Francisco, USA）
  • Year and Date: 2015-03-25 – 2015-03-28
• [Presentation] 子宮体部漿液性腺癌細胞株においてlet-7cは多剤耐性取得機序に関与している (2014)
  • Author(s): 佐藤いずみ、鈴木史彦、永瀬智、高野忠夫、新倉仁、伊藤潔、渡部洋、八重樫伸生
  • Organizer: 第73回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜（横浜）
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] 子宮体部漿液性腺癌におけるmiR-101の機能解析 (2014)
  • Author(s): 鈴木史彦、永瀬智、渡部洋、佐藤いずみ、宇都宮裕貴、新倉仁、笹野公伸、八重樫伸生
  • Organizer: 第73回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜（横浜）
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] ABCトランスポーターからみた子宮体部漿液性腺癌の薬剤獲得耐性メカニズム (2014)
  • Author(s): 鈴木史彦、永瀬智、佐藤いずみ、宇都宮裕貴、海法道子、徳永英樹、伊藤潔、新倉仁、高野忠夫、渡部洋、笹野公伸、八重樫伸生
  • Organizer: 第66回日本産科婦人科学会学術講演会
  • Place of Presentation: 東京国際フォーラム（東京）
  • Year and Date: 2014-04-18 – 2014-04-20
• [Presentation] 子宮体部漿液性腺癌薬剤耐性株におけるマイクロRNAの網羅的発現解析およびmiR-200 familyの発現解析 (2014)
  • Author(s): 佐藤いずみ、永瀬智、鈴木史彦、永井智之、田中創大、海法道子、徳永英樹、高野忠夫、新倉仁、伊藤潔、渡部洋、八重樫伸生
  • Organizer: 第66回日本産科婦人科学会学術講演会
  • Place of Presentation: 東京国際フォーラム（東京）
  • Year and Date: 2014-04-18 – 2014-04-20
• [Presentation] 子宮体部漿液性腺癌に対するmiR-101を用いた分子標的治療の可能性
  • Author(s): 鈴木史彦、永瀬智、佐藤いずみ、宇都宮裕貴、新倉 仁、渡部洋、笹野公伸、八重樫伸生
  • Organizer: 第１３回日本婦人科がん分子標的研究会
  • Place of Presentation: 鳥取
• [Presentation] 子宮体部漿液性腺癌におけるマイクロＲＮＡの発現異常
  • Author(s): 永瀬智
  • Organizer: 熊本大学産婦人科セミナー
  • Place of Presentation: 熊本
  • Invited