Alterations of microRNA associated with cancer-related genes

• Project/Area Number: 19590363
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Human pathology
• Research Institution: Iwate Medical University
• Principal Investigator: MAESAWA Chihaya Iwate Medical University, 医学部, 教授 (10326647)
• Co-Investigator(Kenkyū-buntansha): WAKABAYASHI Go 岩手医科大学, 医学部, 教授 (50175064)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2007: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: microRNA / がん遺伝子 / がん抑制遺伝子 / エピゲノム / 甲状腺 / 未分化癌 / 乳頭癌 / hTERT / 不死化 / microarray / microarra

Research Abstract

近年, 蛋白質をコードしない遺伝子(non-coding RNA ; ncRNA)が機能的RNAとして振る舞うことが注目されている. 特にmiRNAは, 全蛋白質の10-30%程度を制御下にしているとの試算もなされている. miRNAはgenetic/epigenetic以外の第三の遺伝子制御機構として, 細胞特異的な遺伝子発現に関与している可能性がある. 本研究では, 複数の癌腫において, 生物学的特性の形成に重要なmiRNAの発現異常を解析した. 甲状腺癌では, 末分化癌におけるmiR-138の極端な発現低下が確認された. miR-138の発現低下はhTERT遺伝子産物の発現を誘導し, 甲状腺末分化癌のアグレッシブな生物学的特性を反映するものと考えられた. また, 約半数の骨肉腫で, miR-127の発現低下が認められた. miR-127の発現低下はBCL6の過剰発現を誘導した. miR-127はエピジェネティックな発現の制御を受けており, miR-127の発現低下により誘導されたBCL6陽性骨肉腫では, 予後不良の傾向にあった. 悪性黒色腫ではmiR-211の発現低下が認められ, これはcancer-testis antigenであるPRAMEの発現を誘導していた. PRAME遺伝子産物は白血病では免疫療法の標的遺伝子ともなっており, 治療戦略への応用も考えられた. また当所目的で掲げたmaspin遺伝子のaberrantは発現に関与するmiRNAの特定には至らなかった. 悪性腫瘍には組織型毎に特徴的なmiRNAのプロファイルを示し個々の癌腫の生物学的特性の形成に役立っている. 本研究で特定されたmiRNAsは今後個々の癌腫の治療戦略を考える上に重要な情報を供与するもと考えられた.

Research Products

• [Journal Article] Differential microRNA expression between bone marrow side population cells and hepatocytes in adult mice (2009)
  • Author(s): Nagata Y, Maesawa C, Tada H, Takikawa Y, Yashima-Abo A, Masuda T.
  • Journal Title: Int J Mol Med 24 Pages: 35-43
• [Journal Article] Effect of atorvastatin on microRNA 221/222 expression in endothelial progenitor cells obtained from patients with coronary artery disease (2009)
  • Author(s): Minami Y, Satoh M, Maesawa C, Takahashi Y, Tabuchi T, Itoh T, Nakamura M.
  • Journal Title: Eur J Clin Invest 39 Pages: 359-67
• [Journal Article] Loss of class III beta-tubulin induced by histone deacetylation is associated with chemosensitivity to paclitaxel in malignant melanoma cells. (2009)
  • Author(s): Akasaka K, Maesawa C, et al.
  • Journal Title: J Invest Dermatol 129 Pages: 1516-1526
  • Peer Reviewed
• [Journal Article] Effect of atorvastatin on microRNA 221/222 expression in endothelial progenitor cells obtained from patients with coronary artery disease. (2009)
  • Author(s): Minami Y, Satoh M, Maesawa C, Takahashi Y, Tabuchi T, Itoh T, Nakamura M.
  • Journal Title: Eur J Clin Invest 129 Pages: 369-367
  • Peer Reviewed
• [Journal Article] Downregulation of miR-138 is associated with overexpression of human telomerase reverse transcriptase protein in human anaplastic thyroid carcinoma cell lines (2008)
  • Author(s): Mitomo S, Maesawa C, Ogasawara S, Iwaya T, Shibazaki M, Yashima-Abo A, Kotani K, Oikawa H, Sakurai E, Izutsu N, Kato K, Komatsu H, Ikeda K, Wakabayashi G, Masuda T.
  • Journal Title: Cancer Sci 99 Pages: 280-6
  • NAID: 10024002213
• [Journal Article] Angiotensin II and epidermal growth factor receptor cross-talk mediated by a disintegrin and metalloprotease accelerates tumor cell proliferation of hepatocellular carcinoma cell lines. (2008)
  • Author(s): Itabashi H, Maesawa C, Masuda T.
  • Journal Title: Hepatol Res 38 Pages: 601-613
  • NAID: 10024148920
  • Peer Reviewed
• [Journal Article] Epigenetic modification is involved in aberrant expression of class III beta-tubulin, TUBB3, in ovarian cancer cells. (2008)
  • Author(s): Izutsu N, Maesawa C, Masuda T., et al
  • Journal Title: Int J Oncol 32 Pages: 1227-1235
  • Peer Reviewed
• [Journal Article] Downregulation of miR-138 is associated with overexpression of human telomerase reverse transcriptase protein in human anaplastic thyroid carcinoma cell lines (2008)
  • Author(s): Mitomo S, Maesawa C, Ogasawara S, Iwaya T, Shibazaki M, Yashima-Abo A, Kotani K, Oikawa H, Sakurai E, Izutsu N, Kato K, Komatsu H, Ikeda K, Wakabayashi G, Masuda T.
  • Journal Title: Cancer Sci 106 Pages: 354-360
  • NAID: 10024002213
  • Peer Reviewed
• [Journal Article] Tomoyuki Masuda. Down-regulation of microRNA-211 is involved in expression of preferentially expressed antigen of melanoma(PRAME)in melanoma cells
  • Author(s): Sakurai E, Maesawa C, Oikawa H, Akasaka K, Tsunoda K Miyamoto A, Muraoka S, Tada H, Takahashi K, Kudo K, Akasaka T
  • Journal Title: Br J Dermatol (in press)
• [Journal Article] Down-regulation of microRNA-127 is associated with overexpression of BCL6 protein in osteosarcoma cells
  • Author(s): Masuda S, Maesawa C, Nagata Y, Nishida J, Satoh T, Tada T, Sakurai E, Miyamoto A, Muraoka S, Shoji Kanno S, Naraba H, Kitagawa T, Shimamura T, Kudo K, Yonezawa Y, Masuda T.
  • Journal Title: Lab Invest (in press)
• [Presentation] 悪性黒色における癌精巣抗原PRAMEの発現に関わるmiR-211の役割 (2008)
  • Author(s): 前沢千早, 櫻井英一, 赤坂季代美, 増田友之
  • Organizer: 第97回日本病理学会総会
  • Place of Presentation: 金沢
• [Presentation] Down-regulation of microRNA-127 is associated with overexpression of BCL6 protein in osteosarcoma cells. (2007)
  • Author(s): Maesawa C, Masuda S, Masuda T
  • Organizer: 第66回日本癌学会総会
  • Place of Presentation: 横浜
• [Presentation] Expression of markers of progenitors in thyroid cancer (2007)
  • Author(s): Ogasawara S, Maesawa C, Tomisawa Y, Iwaya T, Nishizuka S, Matsuo T, Yamamoto M, Masuda T, Wkabayashi G.
  • Organizer: 第66回日本癌学会総会
  • Place of Presentation: 横浜
• [Presentation] Down-regulation of miRNA-138 is associated with overexpression of hTERT protein in anaplastic thyroid carcinoma (2007)
  • Author(s): Mitomo S, Maesawa C, Ogasawa S, Wakabayashi G, Masuda T
  • Organizer: 第66回日本癌学会総会
  • Place of Presentation: 横浜