oncomir and its target gene in endometrial carcinogenesis

• Project/Area Number: 25670690
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Obstetrics and gynecology
• Research Institution: Hokkaido University
• Principal Investigator: WATARI Hidemichi 北海道大学, 大学病院, 講師 (10344508)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: endometrial cancer / micro RNA / miR-31 / LATS2 / hippo pathway / microRNA / hippo signaling pathway / cyclinD1 / microRNA-31

Outline of Final Research Achievements

The overexpression of microRNA-31 (miR-31) significantly promoted anchorage-independent growth in vitro and significantly increased the tumor forming potential in vivo in endometrial cancer cells. miR-31 significantly suppressed the luciferase activity of mRNA combined with the LATS2 3’-UTR and consequently promoted the translocation of YAP1, a key molecule in the Hippo pathway, into the nucleus. Meanwhile, the nuclear localization of YAP1 increased the transcription of cyclinD1. Furthermore, the expression levels of miR-31 were significantly increased in the patients (n = 27) with a high risk of recurrence compared to that observed in the low-risk patients (n = 7), and this higher expression correlated with a poor survival.
We conclude that miR-31 functions as an oncogene in endometrial cancer by repressing the hippo pathway. miR-31 is a potential new molecular marker for predicting the risk of recurrence and prognosis of endometrial cancer.

Research Products

• [Journal Article] microRNA 31 functions as an endometrial cancer oncogene by suppressing Hippo tumor suppressor pathway. (2014)
  • Author(s): Mitamura T, Watari H, Wang L, Kanno H, Kitagawa M, Hassan MK, Kimura T, Tanino M, Nishihara H, Tanaka S, Sakuragi N.
  • Journal Title: Molecular Cancer Volume: 13 Issue: 1 Pages: 97-97
  • DOI: 10.1186/1476-4598-13-97
  • NAID: 120005464724
  • Peer Reviewed / Open Access
• [Journal Article] Identification of KLF17 as a novelepithelial to mesenchymal transition inducer via direct activation of TWIST1 in endometrioid endometrial cancer (2014)
  • Author(s): Dong P, Kaneuchi M, Xiong Y, Cao L, Cai M, Liu X, Guo SW, Ju J, Jia N, Konno Y, Watari H, Hosaka M, Sudo S, Sakuragi N.
  • Journal Title: Carcinogenesis Volume: 35 Issue: 4 Pages: 760-768
  • DOI: 10.1093/carcin/bgt369
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] MicroRNA106b modulates epithelial-mesenchymal transition by targeting TWIST1 in invasive endometrial cancer cell lines. (2013)
  • Author(s): Dong P, Kaneuchi M, Watari H, Sudo S, Sakuragi N.
  • Journal Title: Molecular Carcinogenesis Volume: 53 Issue: 5 Pages: 349-359
  • DOI: 10.1002/mc.21983
  • Peer Reviewed
• [Presentation] miR-31は子宮体癌において癌遺伝子として機能する (2014)
  • Author(s): 三田村 卓、渡利 英道、王 磊、菅野 宏美、北川 真紀子、Mohamed K Hassan、 木村 太一、谷野 美智枝、西原 広史、田中 伸哉、櫻木 範明
  • Organizer: 第13回日本婦人科がん分子標的研究会
  • Place of Presentation: 皆生グランドホテル天水（米子市）
• [Book] Current approaches to endometrial cancer (2014)
  • Author(s): Watari H, Dong P, Mitamura T, Fujita H, Sakuragi N.
  • Publisher: Future medicine