Identification of micro RNAs which affected by tumor microenvironments of ovarian cancer and analysis of a potential as a therapeutic target

2013 Fiscal Year Final Research Report

• Project/Area Number: 23592447
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Osaka University
• Principal Investigator: SAWADA Kenjiro 大阪大学, 医学(系)研究科(研究院), 講師 (00452392)
• Co-Investigator(Kenkyū-buntansha): MABUCHI Seiji 大阪大学, 医学系研究科, 助教 (00452441) ; ISOBE Aki 大阪大学, 医学系研究科, 助教 (60397619) ; HASHIMOTO Kae 大阪大学, 医学系研究科, 助教 (90612078)
• Project Period (FY): 2011 – 2013
• Keywords: 卵巣癌 / 腹膜播種 / 腹膜中皮細胞 / マイクロRNA

Research Abstract

During the dissemination of ovarian cancer cells, cells are floating in the peritoneal cavity without vascular supply and exposed in hypoxic conditions. We suggest that hypoxic stimuli affect ovarian cancer cell behavior. In this study, we screened miRNAs which expression were altered under hypoxic condition. miRNA PCR arrays revealed that the expression of miR-199a-3p decreased under hypoxic conditions. In silico analyses led us to consider MET is one of the target genes of miR-199a-3p. miR-199a-3p expression was inversely correlated with c-Met expression in ovarian cancer cells. Transfection of precursor miR-199a-3p into ovarian cancer cells reduced c-Met expression followed by the inhibition of the proliferation, adhesion and invasion. In an ovarian cancer xenograft model, the enforced expression of miR-199a-3p in SKOV3 cells significantly suppressed peritoneal dissemination. Thus we suggested that miR-199a-3p is a potential target for treating ovarian cancer dissemination.

Research Products

• [Journal Article] miR-92a Inhibits Peritoneal Dissemination of Ovarian Cancer Cells by Inhibiting Integrin alpha5 Expression (2013)
  • Author(s): Ohyagi-Hara, C. Sawada, K. Kamiura, S. Tomita, Y. Isobe, A. Hashimoto, K. Kinose, Y. Mabuchi, S. Hisamatsu, T. Takahashi, T. Kumasawa, K. Nagata, S. Morishige, K. I. Lengyel, E. Kurachi, H. Kimura, T.
  • Journal Title: Am J Pathol Volume: 182 Pages: 1876-1889
• [Journal Article] Estradiol and raloxifene induce the proliferation of osteoblasts through G-protein-coupled receptor GPR30 (2013)
  • Author(s): Noda-Seino, H. Sawada, K. Hayakawa, J. Ohyagi-Hara, C. Mabuchi, S. Takahashi, K. Nishio, Y. Sakata, M. Kurachi, H. Kimura, T
  • Journal Title: J Endocrinol Invest Volume: 36 Pages: 21-27
• [Journal Article] Targeting interleukin-6 receptor inhibits preterm delivery induced by inflammation Wakabayashi (2013)
  • Author(s): A. Sawada, K. Nakayama, M. Toda, A. Kimoto, A. Mabuchi, S. Kinose, Y. Nakamura, K. Takahashi, K. Kurachi, H. Kimura, T
  • Journal Title: Mol Hum Reprod Volume: 19 Pages: 718-726
• [Presentation] Hypoxia related microRNA, miR-199a-3p, inhibits ovarian cancer progression through the suppression of c-Met expression (2013)
  • Author(s): Kinose, Y. Sawada, K. Mabuchi, S. Morishige, K. Kimura, T
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 20131003-05