Identification of microRNA which regulates peritoneal dissemination of ovarian cancer

• Project/Area Number: 21791555
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Obstetrics and gynecology
• Research Institution: Osaka University
• Principal Investigator: SAWADA Kenjiro Osaka University, 医学部附属病院, 助教 (00452392)
• Project Period (FY): 2009 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2009: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: マイクロRNA / 腹膜播種 / 卵巣癌 / インテグリン / 播種 / インテグリンa5

Research Abstract

Ovarian cancer is a highly metastatic characterized by widespread peritoneal dissemination and ascites, and is the leading cause of death from gynecological malignancy. We have previously identified integrinα5 as a new target in ovarian cancer treatment by inhibiting peritoneal dissemination. Our aim is to identify new microRNA which regulates the expression of integrinα5 and analyze the therapeutic potential of targeting of its microRNA. Based on the microRNA algorism search, we identified hsa-mir-92a as a candidate. Hsa-mir-92a is little expressed in ovarian cancer cells which express high level of integrinα5, whereas hsa-mir-92a is highly expressed in RMUG-S cells which do not express integrinα5. Transfection of precursor mir-92a reduced integrinα5 expression in ovarian cancer cells, accompanied by the inhibition of cell adhesion and invasion. Those results suggested targeting hsa-mir-92a could be a promising therapy for a subset of ovarian cancer patients by inhibiting integrin α5 expression.

Research Products

• [Journal Article] Ligand-independent activation of c-Met by fibronectin and α5β1-integrin regulates ovarian cancer invasion and metastasis. (2011)
  • Author(s): Mitra AK, Sawada K, Tiwari P, Mui K, Gwin K, Lengyel E.
  • Journal Title: Oncogene 30(13) Pages: 1566-76
• [Journal Article] CD95 promotes tumour growth. (2010)
  • Author(s): Chen L, Park SM, Tumanov AV, Hau A, Sawada K., et al.
  • Journal Title: Nature Volume: 465 Pages: 492-496
  • Peer Reviewed
• [Journal Article] Up-regulation of alpha5-integrin by E-cadherin loss in hypoxia and its key role in the migration of extravillous trophoblast cells during early implantation. (2009)
  • Author(s): Arimoto-Ishida E, Sakata M, Sawada K, Nakayama M, Nishimoto F, Mabuchi S, Takeda T, Yamamoto T, Isobe A, Okamoto Y, Lengyel E, Suehara N, Morishige K, Kimura T.
  • Journal Title: Endocrinology 150(9) Pages: 4306-15
• [Journal Article] Fasudil inhibits lysophosphatidic acid-induced invasiveness of human ovarian cancer cells. (2009)
  • Author(s): Ogata S, Morishige K, Sawada K, et al.
  • Journal Title: Int J Gynecol Cancer 19 Pages: 1473-1480
  • Peer Reviewed
• [Journal Article] Up-regulation of alpha5-integrin by E-cadherin loss in hypoxia and itskey role in the migration of extravillous trophoblast cells during early implantation. (2009)
  • Author(s): Arimoto-Ishida E, Sakata M, Sawada K, et al.
  • Journal Title: Endocrinology 150 Pages: 4306-4315
  • Peer Reviewed
• [Presentation] Identification of microRNA which regulates peritoneal dissemination of ovarian cancer (2010)
  • Author(s): Ohyagi, C.Sawada, K.Mabuchi, S.Kimura, T.
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪
  • Year and Date: 2010-09-22
• [Presentation] Identification of microRNA which regulates peritoneal dissemination of ovarian cancer. (2010)
  • Author(s): Ohyagi C, Sawada K, Mabuchi S, Kimura T.
  • Organizer: In:第69回日本癌学会学術総会
  • Place of Presentation: 大阪