A role of microRNA-205 associated with delta-Np63 in oral squamous cell carcinoma

• Project/Area Number: 18K17200
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 57060:Surgical dentistry-related
• Research Institution: Kyushu University
• Principal Investigator: Hashiguchi Yuma 九州大学, 歯学研究院, 共同研究員 (80805268)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: OSCC / EMT / microRNA / miR-205 / ZEB / p63 / ΔNp63 / ZEB1 / ZEB2 / ΔNp63β / miRNA / cancer

Outline of Final Research Achievements

Recently, epitherial-mesenchymal transition (EMT) plays an important role in the process of invasion and metastasis of cancer. We have shown that EMT is induced by ΔNp63β, a splicing variant of ΔNp63, in oral squamous cell carcinoma (OSCC). Furthermore, recent findings suggest that microRNA (miRNA) is involved in the molecular mechanism. We found that miR-205 plays an important role downstream of ΔNp63 and regulates its expression by targeting mesenchymal markers such as ZEB1 and ZEB2, which are associated with EMT.

Academic Significance and Societal Importance of the Research Achievements

本研究は口腔扁平上皮癌における浸潤・転移の分子メカニズムの一部にΔNp63と関連してmicroRNA（miR-205）が関与している可能性を示した。癌の転移は生命予後を左右する重要な要素で有り、口腔癌においても頸部リンパ節転移や他臓器への遠隔転移は予後に大きく関与し、やはりその制御は未だ十分ではない。本研究のように癌の浸潤・転移の分子メカニズムを部分的にでも明らかにしていくことにより、新たな標的として治療方法を確立することで、口腔癌の治療成績のさらなる向上へ役立てることが出来ると考えている。

Research Products

• [Journal Article] Cytokeratin 19 as a biomarker of highly invasive oral squamous cell carcinoma with metastatic potential (2020)
  • Author(s): Tanaka Shoichi、Kawano Shintaro、Hattori Taichi、Matsubara Ryota、Sakamoto Taiki、Hashiguchi Yuma、Kaneko Naoki、Mikami Yurie、Morioka Masahiko、Maruse Yasuyuki、Kitamura Ryoji、Hamada Eiki、Hiwatashi Megumi、Oobu Kazunari、Kiyoshima Tamotsu、Nakamura Seiji
  • Journal Title: Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology Volume: 32 Issue: 1 Pages: 1-7
  • DOI: 10.1016/j.ajoms.2019.10.007
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Tumor-suppressive roles of ΔNp63β-miR-205 axis in epithelial-mesenchymal transition of oral squamous cell carcinoma via targeting ZEB1 and ZEB2. (2017)
  • Author(s): Yuma Hashiguchi, Shintaro Kawano, Yuichi Goto, Kaori Yasuda, Naoki Kaneko, Taiki Sakamoto, Ryota Matsubara, Teppei Jinno, Yasuyuki Maruse, Hideaki Tanaka, Masahiko Morioka, Taichi Hattori, Shoichi Tanaka, Tamotsu Kiyoshima, Seiji Nakamura
  • Journal Title: Journal of Cellular Physiology Volume: － Issue: 10 Pages: 6565-6577
  • DOI: 10.1002/jcp.26267
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] 口腔扁平上皮癌におけるKRT19の発現に関する研究～上皮-間葉転換におけるΔNp63との関わりについて～ (2019)
  • Author(s): 田中翔一、川野真太郎、松原良太、坂本泰基、金子直樹、橋口有真、服部多市、大部一成、中村誠司
  • Organizer: 第37回 日本口腔腫瘍学会総会・学術大会
• [Presentation] 口腔扁平上皮癌におけるΔNp63を介したkallikrein related peptidase （KLK）5の発現と機能について (2019)
  • Author(s): 服部 多市・川野 真太郎・松原 良太・坂本 泰基・橋口 有真・金子 直樹・田中 翔一・大部 一成・中村 誠司
  • Organizer: 第73回 日本口腔科学会学術集会
• [Presentation] ΔNp63を介した口腔扁平上皮癌の上皮間葉転換におけるprotease-activated receptor 1の関与 (2019)
  • Author(s): 服部 多市・川野 真太郎・金子 直樹・田中 翔一・坂本 泰基・橋口 有真・丸瀬 靖之・森岡 政彦・濱田 栄樹・中村 誠司
  • Organizer: 第64回 日本口腔外科学会総会・学術大会
• [Presentation] Involvement of increased cytokeratin 19 expression via down-regulation of ΔNp63 in invasion and metastasis of oral squamous cell carcinomacarcinoma (2019)
  • Author(s): Shoichi Tanaka, Shintaro Kawano, Taichi Hattori, Taiki Sakamoto, Yuma Hashiguchi, Naoki Kaneko, Yurie Mikami, Masahiko Morioka, Yasuyuki Maruse, Ryoji Kitamura, Eiki Hamada, Megumi Hiwatashi, Kazunari Oobu, Tamotsu Kiyoshima, and Seiji Nakamura
  • Organizer: 7th World Congress of the International Academy of Oral Oncology（IAOO）
  • Int'l Joint Research
• [Presentation] cytokeratin 19の発現亢進が口腔扁平上皮癌の浸潤・遊走能に与える影響～ΔNp63との関わりについて～ (2019)
  • Author(s): 田中翔一・川野真太郎・服部多市・坂本泰基・金子直樹・橋口有真・大部一成・中村誠司
  • Organizer: 第29回 日本口腔内科学会