Identification of microRNA-mediated networks in salivary duct carcinoma

• Project/Area Number: 25861528
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Otorhinolaryngology
• Research Institution: Chiba University
• Principal Investigator: KINOSHITA Takashi 千葉大学, 医学部附属病院, 医員 (00648462)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: マイクロRNA / 頭頸部癌 / 唾液腺導管癌 / microrna / マイクロアレイ

Outline of Final Research Achievements

Salivary duct carcinoma (SDC) is an aggressive disease with poor prognosis. Despite of multimodal therapies (surgical resection with neck dissection, radiation and chemotherapy), SDC frequently occurs local recurrence, and metastasizes to distant organs, such as lung, bone and liver. Most patients die within four years of diagnosis. There is no established treatment protocol for this disease even now. In this study, we constructed gene expression signatures (messenger RNA and microRNA) of SDC and tried to identify the molecular mechanisms that characterize of the disease. Our expression data revealed that ECM-related genes were significantly upregulated in SDC specimens. Moreover, microRNA-29b was significantly reduced in SDC and this microRNA act as a tumor suppressor in cancer cells. Interestingly, microRNA-29b regulates ECM-related genes by in silico analysis. Identification of novel mRNA/microRNA networks could provide new insights into underlying molecular mechanisms of SDC.

Research Products

• [Journal Article] MicroRNA expression signature of oral squamous cell carcinoma: functional role of microRNA-26a/b in the modulation of novel cancer pathways. (2015)
  • Author(s): Fukumoto I, Hanazawa T, Kinoshita T, Kikkawa N, Koshizuka K, Goto Y, Nishikawa R, Chiyomaru T, Enokida H, Nakagawa M, Okamoto Y, Seki N.
  • Journal Title: Br J Cancer Volume: 112 Issue: 5 Pages: 891-900
  • DOI: 10.1038/bjc.2015.19
  • Peer Reviewed / Open Access
• [Journal Article] Identification of tumour suppressive microRNA-451a in hypopharyngeal squamous cell carcinoma based on microRNA expression signature (2014)
  • Author(s): Fukumoto I, Kinoshita T, Hanazawa T, Kikkawa N, Chiyomaru T, Enokida H, Yamamoto N, Goto Y, Nishikawa R, Nakagawa M, Okamoto Y, Seki N.
  • Journal Title: British Journal of Cancer Volume: 111 Issue: 2 Pages: 386-394
  • DOI: 10.1038/bjc.2014.293
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] microRNA-504 inhibits cancer cell proliferation via targeting CDK6 in hypopharyngeal squamous cell carcinoma. (2014)
  • Author(s): Kikkawa N, Kinoshita T, Nohata N, Hanazawa T, Yamamoto N, Fukumoto I, Chiyomaru T, Enokida H, Nakagawa M, Okamoto Y, Seki N.
  • Journal Title: Int J Oncol. Volume: 44(6) Issue: 6 Pages: 2085-92
  • DOI: 10.3892/ijo.2014.2349
  • Peer Reviewed / Open Access
• [Journal Article] Tumour-suppressive microRNA-29s inhibit cancer cell migration and invasion by targeting laminin-integrin signalling in head and neck squamous cell carcinoma. (2013)
  • Author(s): Kinoshita T, Nohata N, Hanazawa T, Kikkawa N, Yamamoto N, Yoshino H, Itesako T, Enokida H, Nakagawa M, Okamoto Y, Seki N.
  • Journal Title: Br J Cancer Volume: 109 Issue: 10 Pages: 2636-2645
  • DOI: 10.1038/bjc.2013.607
  • Peer Reviewed
• [Journal Article] Tumour-suppressive microRNA-874 contributes to cell proliferation through targeting of histone deacetylase 1 in head and neck squamous cell carcinoma. (2013)
  • Author(s): Nohata N, Hanazawa T, Kinoshita T, Inamine A, Kikkawa N, Itesako T, Yoshino H, Enokida H, Nakagawa M, Okamoto Y, Seki N.
  • Journal Title: Br J Cancer Volume: 108 Issue: 8 Pages: 1648-1658
  • DOI: 10.1038/bjc.2013.122
  • Peer Reviewed
• [Presentation] 下咽頭癌マイクロRNA発現プロファイルに基づく、癌抑制型マイクロRNAの探索とマイクロRNAが制御する標的癌遺伝子の同定 (2014)
  • Author(s): 木下崇、福本一郎、吉川直子、花澤豊行、岡本美孝、関直彦
  • Organizer: 第38回日本頭頸部癌学会学術講演会
  • Place of Presentation: 東京都江東区 東京ファッションタウンビル
  • Year and Date: 2014-06-12 – 2014-06-13
• [Presentation] 頭頸部扁平上皮癌におけるmicroRNA-29sによるラミニン・インテグリンシグナル制御機構 (2014)
  • Author(s): 木下崇、花澤豊行、野畑二次郎、吉川直子、岡本美孝
  • Organizer: 第115回日本耳鼻咽喉科学会総会・学術講演会
  • Place of Presentation: 福岡市 ヒルトン福岡シーホーク
  • Year and Date: 2014-05-14 – 2014-05-17
• [Presentation] Tumor suppressive microRNAs (miR-29s/miR-218) regulate laminin-integrin signaling in head and neck squamous cell carcinoma (2014)
  • Author(s): Takashi Kinoshita, Nijiro Nohata, Toyoyuki Hanazawa, Naoko Kikkawa, Noriko Yamamoto, Hirofumi Yoshino, Toshihiko Itesako, Hideki Enokida, Masayuki Nakagawa, Yoshitaka Okamoto, Naohiko Seki
  • Organizer: American Association of Cancer Research Annual Meeting 2014
  • Place of Presentation: San Diego Convention Center, San Diego, CA, USA
  • Year and Date: 2014-04-06 – 2014-04-11
• [Presentation] 頭頸部扁平上皮癌におけるmicroRNA-218の機能解析： ラミニン・インテグリン分子ネットワークの抑制機構の解明 (2013)
  • Author(s): 木下崇、花澤豊行、野畑二次郎、吉川直子、茶薗英明、岡本美孝、関直彦
  • Organizer: 第37回日本頭頸部癌学会
  • Place of Presentation: 東京都 京王プラザホテル
• [Presentation] Tumor suppressive microRNA-218 targeting focal adhesion pathway in head and neck squamous cell carcinoma (2013)
  • Author(s): Takashi Kinoshita, Toyoyuki Hanazawa, Nijiro Nohata, Naoko Kikkawa, Hideki Enokida, Hirofumi Yoshino, Masayuki Nakagawa, Yoshitaka Okamoto, Naohiko Seki
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: 神奈川県 パシフィコ横浜
• [Remarks] 千葉大学大学院医学研究院 先端応用医学講座 機能ゲノム学ホームページ
  • URL: http://genomejet.jp
• [Remarks] 千葉大学大学院医学研究院 機能ゲノム学ホームページ
  • URL: http://genomejet.jp/