Identification of tumor suppressive nucleic acid medicine in maxillary sinus squamous cell carcionma

• Project/Area Number: 23592505
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Otorhinolaryngology
• Research Institution: Chiba University
• Principal Investigator: HANAZAWA Toyoyuki 千葉大学, 医学(系)研究科(研究院), 准教授 (90272327)
• Co-Investigator(Kenkyū-buntansha): SEKI Naohiko 千葉大学, 大学院医学研究院, 准教授 (50345013)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: microRNA / 上顎洞癌 / 癌抑制遺伝子 / miR-874 / HDAC1 / 上顎癌 / マイクロRNA / がん / ゲノム

Research Abstract

Our recent studies of microRNA (miRNA) expression signature of maxillary sinus squamous cell carcinoma (MSSCC) demonstrated that microRNA-874 (miR-874) was significantly downregulated in cancer tissues, suggesting miR-874 function as a tumor suppressor. Restoration of mature miR-874 significantly inhibited cancer cell proliferation and induced apoptosis. Expression data of miR-874 transfectants and in silico analysis demonstrated that histone deacetylase 1 (HDAC1) was a direct target of miR-874 regulation. Silencing of the HDAC1 gene significantly inhibited cell proliferation and induced G2/M arrest and cell apoptosis in cancer cell. Downregulation of miR-874 was a frequent event in HNSCC. miR-874 acted as a tumor suppressor and directly targeted HDAC1. Recognition of tumor-suppressive miRNA-mediated cancer pathways provides new insights into the potential mechanisms of MSSCC oncogenesis and suggests novel therapeutic strategies for the disease.

Research Products

• [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
• [Journal Article] Tumor suppressive microRNA-375 regulates lactate dehydrogenase B in maxillary sinus squamous cell carcinoma (2012)
  • Author(s): Kinoshita T, Nohata N, Yoshino H, Hanazawa T, Kikkawa N, Fujimura L, Chiyomaru T, Kawakami K, Enokida H, Nakagawa M, Okamoto Y, Seki N.
  • Journal Title: Int J Oncol Volume: 40 Pages: 185-93
  • DOI: 10.3892/ijo.2011.1196
  • Peer Reviewed
• [Journal Article] The functional significance of microRNA-375 in human squamous cell carcinoma: aberrant expression and effects on cancer pathways. (2012)
  • Author(s): Kinoshita T, Hanazawa T, Nohata N, Okamoto Y, Seki N
  • Journal Title: J Hum Genet. Volume: 57 Issue: 9 Pages: 556-63
  • DOI: 10.1038/jhg.2012.75
  • NAID: 10031056783
  • Peer Reviewed
• [Journal Article] microRNA-1/133a and microRNA-206/133b clusters: dysregulation and functional roles in human cancers. (2012)
  • Author(s): Nohata N, Hanazawa T, Enokida H, Seki N
  • Journal Title: Oncotarget Volume: 3 Pages: 9-21
  • Peer Reviewed
• [Journal Article] Tumor suppressive microRNA-133a regulates novel targets : moesin contributes to cancer cell proliferation and invasion in head and neck squamous cell carcinoma (2012)
  • Author(s): Takashi Kinoshita
  • Journal Title: Biochemical and biophysical research communications Volume: 418 Issue: 2 Pages: 378-83
  • DOI: 10.1016/j.bbrc.2012.01.030
  • Peer Reviewed
• [Journal Article] Actin-related protein 2/3 complex subunit 5 (ARPC5) contributes to cell migration and invasion and is directly regulated by tumor-suppressive microRNA-133a in head and neck squamous cell carcinoma (2012)
  • Author(s): Kinoshita T, Nohata N, Watanabe-Takano H, Yoshino H, Hidaka H, Fujimura L, Fuse M, Yamasaki T, Enokida H, Nakagawa M, Hanazawa T, Okamoto Y, Seki N.
  • Journal Title: Int. J. Oncol Volume: (印刷中) Pages: 1770-8
  • DOI: 10.3892/ijo.2012.1390
  • Peer Reviewed
• [Journal Article] Tumor suppressive microRNA-218 inhibits cancer cell migration and invasion through targeting laminin-332 in head and neck squamous cell carcinoma. (2012)
  • Author(s): Kinoshita T, Hanazawa T, Nohata N, Kikkawa N, Enokida H, Yoshino H, Yamasaki T, Hidaka H, Nakagawa M, Okamoto Y, Seki N.
  • Journal Title: Oncotarget Volume: 3 Pages: 1386-400
  • Peer Reviewed
• [Journal Article] Tumor suppressive microRNA-375 regulates lactate dehydrogenase B in maxillary sinus squamous cell carcinoma. (2012)
  • Author(s): Kinoshita T, Hanazawa T, et al.
  • Journal Title: Int J Oncol Volume: 40 Pages: 185-193
  • Peer Reviewed
• [Journal Article] Tumour suppressive microRNA-874 regulates novel cancer networks in maxillary sinus squamous cell carcinoma (2011)
  • Author(s): Nijiro Nohata
  • Journal Title: British journal of cancer Volume: 105 Issue: 6 Pages: 833-41
  • DOI: 10.1038/bjc.2011.311
  • Peer Reviewed
• [Journal Article] Identification of novel molecular targets regulated by tumor suppressive miR-1/miR-133a in maxillary sinus squamous cell carcinoma (2011)
  • Author(s): Nijiro Nohata
  • Journal Title: International journal of oncology Volume: 39 Pages: 1099-107
  • DOI: 10.3892/ijo.2011.1096
  • Peer Reviewed
• [Journal Article] Tumour suppressive microRNA-874 regulates novel cancer networks in maxillary sinus squamous cell carcinoma. (2011)
  • Author(s): Nohata N, Hanazawa T, et al.
  • Journal Title: Br J Cancer Volume: 105 Pages: 833-841
  • Peer Reviewed
• [Presentation] Tumor suppressive microRNA-218 inhibits cancer cell migration and invasion through targeting laminin-332 in head and neck squamous cell carcinoma (2013)
  • Author(s): Takashi Kinoshita, Toyoyuki Hanazawa, Nijiro Nohata, Naoko Kikkawa, Noriko Yamamoto, Hideki Enokida, Hirofumi Yoshino, Takeshi Yamasaki, Hideo Hidaka, Masayuki Nakagawa, Yoshitaka Okamoto, Naohiko Seki
  • Organizer: AACR Annual 104th Meeting
  • Place of Presentation: Washington, DC, USA)
• [Presentation] Tumor suppressive microRNA-1 and microRNA-133a cluster regulating molecular targets in head and neck squamous cell carcinoma (2012)
  • Author(s): Nijiro Nohata, Toyoyuki Hanazawa, Takashi Kinoshita, Naoko Kikkawa, Daiju Sakurai, Miki Fuse, Hirofumi Yoshino, Hideki Enokida, Masayuki Nakagawa, Yoshitaka Okamoto, Naohiko Seki
  • Organizer: 8th International Conference on Head and Neck Cancer
  • Place of Presentation: Toronto, ON, Canada
• [Presentation] 癌抑制型microRNA-874が制御する頭頸部扁平上皮癌の新規分子ネットワークの解明 (2012)
  • Author(s): 花澤豊行、野畑二次郎、木下崇、吉川直子、堅田浩司、茶薗英明、岡本美孝、関直彦
  • Organizer: 第36回日本頭頸部癌学会学術講演会
  • Place of Presentation: 島根県民会館島根
• [Presentation] 癌抑制型microRNA-375が制御する分子ネットワークの解明と頭頸部扁平上皮癌新規治療戦略の開発 (2012)
  • Author(s): 花澤豊行、野畑二次郎、木下崇、吉川直子、鈴木誉、茶薗英明、櫻井大樹、岡本美孝
  • Organizer: 第113回日本耳鼻咽喉科学会学術講演会
  • Place of Presentation: 朱鷺メッセ新潟
• [Presentation] microRNA-874 as a tumor suppressor in maxillary sinus squamous cell carcinoma based on microRNA expression signature (2012)
  • Author(s): Toyoyuki Hanazawa, Nijiro Nohata, Takashi Kinoshita,Naoko Kikkawa,Miki Fuse, Takeshi Chiyomaru, Hirofumi Yoshinoi, Hideki Enokida, Masayuki Nakagawa, Yoshitaka Okamoto, Naohiko Seki
  • Organizer: AACR 103rd Annual Meeting
  • Place of Presentation: Chicago, IL, USA
• [Presentation] 癌抑制型microRNA-874が制御する頭頸部扁平上皮癌の新規分子ネットワークの解明 (2012)
  • Author(s): 花澤豊行、 野畑二次郎、 木下崇、 吉川直子、 堅田浩司、 茶薗英明、 岡本美孝、関直彦
  • Organizer: 第36回日本頭頸部癌学会
  • Place of Presentation: 島根県民会館（島根）
• [Presentation] 癌抑制型microRNA-375が制御する分子ネットワークの解明と頭頸部扁平上皮癌新規治療戦略の開発 (2012)
  • Author(s): 花澤豊行、野畑二次郎、木下崇、吉川直子、鈴木誉、茶薗英明、櫻井大樹、岡本美孝
  • Organizer: 第113回日本耳鼻咽喉科学会
  • Place of Presentation: 朱鷺メッセ（新潟）
• [Presentation] Identification of tumor suppressive microRNAs in maxillary sinus squamous cell carcinoma based on microRNA expression signature (2011)
  • Author(s): Toyoyuki Hanazawa, Nijiro Nohata, Naoko Kikkawa, Akihiro Katayama, Yasuaki Harabuchi, Yoshitaka Okamoto, Naohiko Seki
  • Organizer: AACR 102nd Annual Meeting
  • Place of Presentation: Orlando, Florida, USA
• [Presentation] Identification of tumor suppressive microRNAs and their target genes in maxillary sinus squamous cell carcinoma (2011)
  • Author(s): 花澤豊行
  • Organizer: 第11回日本台湾耳鼻咽喉科頭頸部外科学会
  • Place of Presentation: 神戸市
• [Remarks]
  • 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/