Exploration of tumor-suppressive microRNAs silenced by DNA hypermethylation in oral cancer

2010 Fiscal Year Final Research Report

• Project/Area Number: 20592136
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Morphological basic dentistry
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: KOZAKI Ken-Ichi Tokyo Medical and Dental University, 難治疾患研究所, 准教授 (50270715)
• Co-Investigator(Kenkyū-buntansha): INAZAWA Johji 東京医科歯科大学, 難治疾患研究所, 教授 (30193551)
• Project Period (FY): 2008 – 2010
• Keywords: 分子腫瘍学

Research Abstract

In this study, we performed function-, methylation- and expression-based screening in oral cancer cell lines, and identified two novel tumor-suppressive microRNAs, miR-218 and miR-585, silenced by DNA hypermethylation in oral cancer. Moreover, we found that Rictor is a novel target of miR-218, suggesting that miR-218 targeting Rictor may provide a novel strategy for the treatment of oral cancer.

Research Products

• [Journal Article] YAP is a candidate oncogene for esophageal squamous-cell carcinoma. (2011)
  • Author(s): Muramatsu, T., Imoto, I., Matsui, T., Kozaki K., Haruki, S., Sudol, M., Shimada, Y., Tsuda, H., Kawano, T., Inazawa J.
  • Journal Title: Carcinogenesis 32(Epub 2010 Nove 26) Pages: 389-365
  • Peer Reviewed
• [Journal Article] Frequent silencing of protocadherin 17, a candidate tumour suppressor for esophageal squamous-cell carcinoma. (2010)
  • Author(s): Haruki, S., Imoto, I., Kozaki K., Matsui, T., Kawachi, H., Komatsu, S., Muramatsu, T., Shimada, Y., Kawano, T., Inazawa J.
  • Journal Title: Carcinogenesis 31(Epub 2010 Mar 3) Pages: 1027-1010
  • Peer Reviewed
• [Journal Article] miR-124 and miR-203 are epigenetically silenced tumor-suppressive microRNAs in hepatocellular carcinoma. (2010)
  • Author(s): Furuta, M., Kozaki K., Tanaka, S., Arii, S., Imoto, I., Inazawa J.
  • Journal Title: Carcinogenesis 31(Epub 2009 Oct 20) Pages: 766-776
  • Peer Reviewed
• [Journal Article] 癌細胞におけるDNAメチル化異常とmicroRNA発現制御 (2010)
  • Author(s): 小崎健一, 稲澤譲治
  • Journal Title: 西胞(株)ニューサイエンス社) 42 Pages: 232-235
• [Journal Article] Identification of PAK4 as a putative target gene for amplification within 19q13.12-q13.2 in oral squamous-cell carcinoma. (2009)
  • Author(s): Begum, A., Imoto, I., Kozaki K., Tsuda, H., Suzuki, E., Amagasa, T., Inazawa J.
  • Journal Title: Cancer Sci. 100 Pages: 1908-1916
  • Peer Reviewed
• [Journal Article] Overexpression of SMYD2 relates to tumor cell proliferation and malignant outcome of esophageal squamous -cell carcinoma. (2009)
  • Author(s): Komatsu, S., Imoto, I., Tsuda, H., Kozaki K., Muramatsu, T., Shimada, Y., Aiko, S., Yoshizumi, Y., Ichikawa, D., Otsuji, E., Inazawa J.
  • Journal Title: Carcinogenesis 30 Pages: 1139-1146
  • Peer Reviewed
• [Journal Article] 癌におけるDNAメチル化異常とmicroRNA発現制御 (2009)
  • Author(s): 小崎健一, 稲澤譲治
  • Journal Title: グノム医学((株)メディカルレビュー社) 9 Pages: 15-22
• [Journal Article] ITCH is a putative target for a novel 20q11.22 amplification detected in anaplastic thyroid carcinoma cells by array-based comparative genomic hybridization. (2008)
  • Author(s): Ishihara, T., Tsuda, H., Hotta, A., Kozaki, K., Yoshida, A., Noh, A.Y., Ito, K., Imoto, I., Inazawa J.
  • Journal Title: Cancer Sci. 99 Pages: 1940-1949
  • Peer Reviewed
• [Journal Article] Expression of cIAP-1 correlates with nodal metastasis in squamous cell carcinoma of the tongue. (2008)
  • Author(s): Qi, S., Mogi, S., Tsuda, H., Tanaka, Y., Kozaki K., Imoto, I., Inazawa J., Hasegawa, S., Omura, K.
  • Journal Title: Int.J.Oral Maxillofac.Surg. 37 Pages: 1047-1053
  • Peer Reviewed
• [Journal Article] Frequent inactivation of a putative conditional tumor-suppressor gene,angiopoietin-like protein 2, in ovarian cancer. (2008)
  • Author(s): Kikuchi, R., Tsuda, H., Kozaki K., Kanai, Y., Kasamatsu, T., Sengoku, K., Hirohashi, S., Inazawa J., Imoto, I.
  • Journal Title: Cancer Res. 68 Pages: 5067-5075
  • Peer Reviewed
• [Journal Article] Frequent silencing of a putative tumor suppressor gene melatonin receptor 1 A (MTNR1A) in oral squamous-cell carcinoma. (2008)
  • Author(s): Nakamura, E., Kozaki K., Tsuda, H., Suzuki, E., Pimkhaokham, A., Yamamoto, G., Irie, T., Tachikawa, T., Amagasa, T., Inazawa J., Imoto, I.
  • Journal Title: Cancer Sci. 99 Pages: 1390-1400
  • Peer Reviewed
• [Journal Article] Exploration of tumor -suppressive microRNAs silenced by DNA hypermethylation in oral cancer. (2008)
  • Author(s): Kozaki K., Imoto, I., Mogi, S., Omura, K., Inazawa J.
  • Journal Title: Cancer Res. 68 Pages: 2094-2105
  • Peer Reviewed
• [Journal Article] 癌幹細胞とmicroRNA (2008)
  • Author(s): 小崎健一, 稲澤譲治
  • Journal Title: 医学のあゆみ((株)医歯薬出版) 227(1) Pages: 2-66
• [Journal Article] がん抑制microRNAと腫瘍特異的DNAメチル化異常 (2008)
  • Author(s): 小崎健一, 稲澤譲治
  • Journal Title: Cancer Frontier((株)医薬ジャーナル社) 10 Pages: 57-63
• [Presentation] Tumor -suppressive microRNAs silenced by DNA hypermethylation in cancer cells.International Sessions "miRNA dysregulation in cancers, and its clinical applications" (2010)
  • Author(s): 小崎健一, 稲澤譲治
  • Organizer: 69th Annual Meeting of Japanese Cancer Association
  • Place of Presentation: Osaka
  • Year and Date: 2010-09-22
• [Presentation] Functional screening of tumor-suppressive microRNAs silenced by DNA. (2010)
  • Author(s): Kozaki K., Uesugi A., Furuta M., Imoto, I., Inazawa J.
  • Organizer: American Association for Cancer Research, 101th Annual Meeting 2010
  • Place of Presentation: Washington, DC
  • Year and Date: 2010-04-19
• [Presentation] 口腔癌における癌抑制遺伝子型microRNAのDNAメチル化異常 (2010)
  • Author(s): 小崎健一、井本逸勢、稲澤譲治
  • Organizer: 第3回硬組織疾患ゲノムセンター・シンポジウム
  • Place of Presentation: 東京
  • Year and Date: 2010-02-16
• [Presentation] Exploration of tumor -suppressive microRNAs silenced by DNA hypermethylation in oral cancer. (2010)
  • Author(s): Kozaki K., Imoto I., Mogi S., Omura K., Inazawa J.
  • Organizer: 8th Joint Conference of the American Association for Cancer Research and Japanese Cancer Association for Cancer Research and Japanese Cancer Association
  • Place of Presentation: Waikoloa, Hawaii
  • Year and Date: 2010-02-08
• [Presentation] 特異的DNA過剰メチル化により発現抑制される癌抑制遺伝子型microRNAの網羅的探索 (2009)
  • Author(s): 小崎健一
  • Organizer: アプライドバイオシステムズセミナー「microRNA研究の最前線～ベールを脱ぐMicroRNAの機能～」
  • Place of Presentation: 東京
  • Year and Date: 20090510-20090512
• [Presentation] Tumor-suppressive microRNAs silenced by DNA hypermethylation. Symposium "Cancer epigenetics-from basic science to clinical practice" (2009)
  • Author(s): 小崎健一, 稲澤譲治
  • Organizer: 68th Annual Meeting of Japanese Cancer Association
  • Place of Presentation: Yokohama
  • Year and Date: 2009-10-02
• [Presentation] DNA過剰メチル化により発現抑制される癌抑制遺伝子型microRNAの機能的探索 (2009)
  • Author(s): 小崎健一、古田繭子、上杉篤史、鶴田智彦、井本逸勢、稲澤譲治
  • Organizer: 日本人類遺伝学会 第54回大会
  • Place of Presentation: 東京
  • Year and Date: 2009-09-25
• [Presentation] 特異的DNA過剰メチル化により発現抑制される癌抑制遺伝子型microRNAの網羅的探索 (2009)
  • Author(s): 小崎健一
  • Organizer: アプライドバイオシステムズセミナー「microRNA研究の最前線～ベールを脱ぐMicroRNAの機能～」
  • Place of Presentation: 大阪
  • Year and Date: 2009-05-28
• [Presentation] 口腔扁平上皮癌において腫瘍特異的DNA過剰メチル化により発現抑制される癌抑制遺伝子型microRNA (2009)
  • Author(s): 小崎健一、井本逸勢、茂木世紀、小村健、稲澤譲治
  • Organizer: 第3回日本エピジェネティクス研究会年会
  • Place of Presentation: 東京
  • Year and Date: 2009-05-23
• [Presentation] 口腔癌における癌抑制microRNAの腫瘍特異的DNAメチル化異常 (2008)
  • Author(s): 小崎健一、井本逸勢、稲澤譲治
  • Organizer: 第2回硬組織疾患ゲノムセンター・シンポジウム
  • Place of Presentation: 東京
  • Year and Date: 2008-11-25
• [Presentation] Silencing of tumor suppressive microRNAs, miR-137 and miR-193a, by tumor-specific DNA hypermethylation in oral cancer. (2008)
  • Author(s): Kozaki K., Imoto, I., Mogi S., Omura K., Inazawa J.
  • Organizer: 67th Annual Meeting of Japanese Cancer Association
  • Place of Presentation: Nagoya
  • Year and Date: 2008-10-29
• [Presentation] がん抑制microRNAと腫瘍特異的DNAメチル化異常 (2008)
  • Author(s): 小崎健一、稲澤譲治
  • Organizer: 日本人類遺伝学会 第53回大会 シンポジウムI「がんオミックス研究の成果とその臨床応用」
  • Place of Presentation: 横浜
  • Year and Date: 2008-09-28
• [Presentation] Silencing of tumor -suppressive microRNAs by DNA hypermethylation in oral squamous cell carcinoma. (2008)
  • Author(s): Kozaki K., Imoto, I., Mogi S., Omura K., Inazawa J.
  • Organizer: American Association for Cancer Research, 99th Annual Meeting 2008
  • Place of Presentation: San Diego, CA
  • Year and Date: 2008-04-16
• [Remarks] ホームページ等
• [Remarks] 東京医科歯科大学 難治疾患研究所 分子細胞遺伝
  • URL: http://www.tmd.ac.jp/mri/cgen/framepage.htm
• [Remarks] 東京医科歯科大学 硬組織疾患ゲノムセンター
  • URL: http://www.tmd.ac.jp/mri/hgr/
• [Patent(Industrial Property Rights)] 癌の検出方法および抑制方法 (2010)
  • Inventor(s): 稲澤譲治、小崎健一、井本逸勢、古田繭子、有井滋樹
  • Industrial Property Rights Holder: 富士フィルム株式会社・国立大学法人東京医科歯科大学
  • Industrial Property Number: 特許,特願2010-046564(P09-034)
  • Filing Date: 2010-03-03
• [Patent(Industrial Property Rights)] 食道癌の検出方法及び抑制剤 (2010)
  • Inventor(s): 稲澤譲治、井本逸勢、小松周平、小崎健一、津田均
  • Industrial Property Rights Holder: 国立大学法人東京医科歯科大学・富士写真フィルム株式会社
  • Industrial Property Number: 特許,特願2009-073998
  • Filing Date: 2010-03-24
  • Overseas
• [Patent(Industrial Property Rights)] 癌の検出方法および癌抑制剤 (2008)
  • Inventor(s): 稲澤譲治、小崎健一、井本逸勢
  • Industrial Property Rights Holder: 国立大学法人東京医科歯科大学・富士写真フィルム株式会社
  • Industrial Property Number: 特許,特願2008-012256(P07-040)
  • Filing Date: 2008-01-23