Investigation of diagnostic marker and drug sensitivity in human renal cell carcinoma cells targeting microRNA

• Project/Area Number: 15K20091
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Urology
• Research Institution: Tottori University
• Principal Investigator: Iwamoto Hideto 鳥取大学, 医学部, 助教 (80621010)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000); Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
• Keywords: microRNA / 腎細胞癌 / スニチニブ抵抗性 / 腫瘍学 / スニチニブ抵抗性株 / microarray

Outline of Final Research Achievements

Microarray analysis and reverse transcription-quantitative polymerase chain reaction revealed that miR-194-5p expression was significantly decreased in sunitinib resistant-ACHN (SR-ACHN) cells when compared with that observed in ACHN cells. Transfection of miR-194-5p, though not with negative control miR, in SR-ACHN cells could significantly inhibit cell proliferation following sunitinib treatment. Western blotting demonstrated that the expression of lysosome-associated membrane protein-2 (LAMP-2), which attenuates the anti-proliferative effect of sunitinib, was significantly higher in SR-ACHN than in ACHN cells. In addition, LAMP-2 expression was suppressed by miR-194-5p transfection in SR-ACHN cells. These data suggested that miR-194-5p downregulation may be associated with sunitinib resistance via the induction of LAMP-2 expression in human RCC.

Research Products

• [Journal Article] Lysosome-associated membrane protein 2 (LAMP-2) expression induced by miR-194-5p down-regulation contributes to sunitinib resistance in human renal cell carcinoma cells. (2017)
  • Author(s): Yumioka T, Osaki M, Sasaki R, Yamaguchi N, Onuma K, Iwamoto H, Morizane S, Honda M, Takenaka A and Okada F.
  • Journal Title: Oncol Lett Volume: 15 Pages: 893-900
  • DOI: 10.3892/ol.2017.7423
  • Peer Reviewed
• [Journal Article] Identification of MicroRNAs Involved in Resistance to Sunitinib in Renal Cell Carcinoma Cells. (2017)
  • Author(s): Yamaguchi N, Osaki M, Onuma K, Yumioka T, Iwamoto H, Sejima T, Kugoh H, Takenaka A, Okada H.
  • Journal Title: Anticancer Research Volume: 37（6） Pages: 2985-2992
  • Peer Reviewed
• [Presentation] 腎細胞癌のスニチニブ耐性を規定するmicroRNAの同定 (2017)
  • Author(s): 山口 徳也
  • Organizer: 第26回 泌尿器科分子・細胞研究会
  • Place of Presentation: 大分県全労済ソレイユ(大分県大分市）
  • Year and Date: 2017-03-10
• [Presentation] Identification of microRNA regulating snitinib resistance in renal cell carcinoma cells. (2017)
  • Author(s): Yamaguchi N, Yumioka T, Onuma K, Iwamoto H, Masago T, Morizane S, Honda M, Osaki M, Okada F, Takenaka A.
  • Organizer: AUA 2017
  • Int'l Joint Research
• [Presentation] Downregulation of miR-194-5p involved in sunitinib resistance in human renal cell carcinoma cell (2017)
  • Author(s): Yumioka T, Osaki M, Yamaguchi N, Kanda Y, Iwamoto H, Onuma K, Morizane S, Honda M, Okada F, Takenaka A
  • Organizer: 第７６回日本癌学会学術総会
• [Presentation] 腎細胞癌のスニチニブ耐性を規定するmicroRNAの同定 (2017)
  • Author(s): 山口徳也、弓岡徹也、小沼邦重、岩本秀人、眞砂俊彦、森實修一、本田正史、尾﨑充彦、岡田 太、武中 篤
  • Organizer: 第26回泌尿器科分子・細胞研究会
• [Presentation] miR-194-5p suppressed cell proliferation by targeting lysosome associated membraneprotain 2 in sunitinib-resistant renal cell carcinoma cells (2017)
  • Author(s): 弓岡徹也、尾崎充彦、山口徳也、小沼邦重、岩本秀人、森實修一、本田正史、岡田 太、武中 篤
  • Organizer: 第69回西日本泌尿器科学会総会
• [Presentation] 腎細胞癌のスニチニブ抵抗性を規定するmicroRNAの同定 (2016)
  • Author(s): 山口 徳也
  • Organizer: 第２５回 泌尿器科分子・細胞研究会
  • Place of Presentation: ハイアットリージェンシー大阪(大阪府大阪市)
  • Year and Date: 2016-02-26