Significance of miRNA in oncogenesis of soft part tumors.

• Project/Area Number: 20590350
• 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: SATOH Takashi Iwate Medical University, 医学部, 准教授 (20170756)
• Co-Investigator(Kenkyū-buntansha): MAESAWA Chihaya 岩手医科大学, 医学部, 教授 (10326647) ; NISHIDA Jun 岩手医科大学, 医, 講師 (20198469)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2008: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 骨肉腫 / 軟骨肉腫 / がん抑制遺伝子 / がん遺伝子 / miRNA / がん抑制遺伝 / 癌抑制遺伝子 / エピジェネティックス

Research Abstract

MicroRNAs (miRNA) are small non-coding RNAs whose aberrations are involved in the initiation and progression of human cancers. To seek unique miRNAs contributing to the development of osteosarcoma, we investigated the global miRNA expression profile. We focused on a commonly down-regulated miRNA, miR-127, and analyzed its relationship with the expression of its potential target, BCL6 protein. We found that 5 of 8 (63%) osteosarcoma cell lines exhibited marked down-regulation of miR-127 in comparison with the remaining cell lines and normal cultured osteoblasts. An inverse correlation between miR-127 and BCL6 protein expression was found in the osteosarcoma cell lines and primary-cultured normal osteoblasts. We demonstrated that overexpression of miR-127 induced a reduction of the BCL6 protein level, and confirmed target specificity between miR-127 and BCL6 by the luciferase reporter assay. Immunohistochemical analysis of BCL6 protein revealed that about half of the primary osteosarcomas (13/25, 52%) showed BCL6 overexpression, whereas normal osteoblasts were completely negative. The disease outcome of BCL6-positive patients was significantly worse than that of BCL6-negative patients (p<0.05). These results suggest that gain of BCL6 protein expression through the repression of miR-127 expression may be partly involved in osteosarcoma development.

Research Products

• [Journal Article] Down-regulation of microRNA-211 is involved in expression of preferentially expressed antigen of melanoma (PRAME) in melanoma cells. (2011)
  • Author(s): E. Sakaurai, C Maesawa
  • Journal Title: Int J Oncol in press
• [Journal Article] Nucleus Accumbens-Associated 1 Contributes to Cortactin Deacetylation and Augments the Migration of Melanoma Cells. (2011)
  • Author(s): K. Tsunoda, H. Oikawa, H. Tada, Y. Tatemichi, S. Muraoka, S. Miura, M. Shibazaki, F. Maeda, K. Takahashi, T. Akasaka, T. Masuda, C. Maesawa
  • Journal Title: J Invest Dermatol in press
• [Journal Article] Nucleus accumbens-associated 1 contributes to cortactin deacetylation and augments the migration of melanoma cells. (2011)
  • Author(s): Tsunoda K
  • Journal Title: J Invest Dermatol Volume: 131(In press)
  • Peer Reviewed
• [Journal Article] Detection of human papillomavirus in a urothelial carcinoma mimicking urethral caruncle. (2010)
  • Author(s): Y. Tatemichi, H. Oikawa, C. Maesawa, J. Ambo, M. Sato, H. Koike, T. Sata, T. Fujioka, T. Masuda
  • Journal Title: Int J Urol 17 Pages: 189-191
  • NAID: 10027257188
• [Journal Article] Association of the TNF-{alpha}-C-857T polymorphism with resistance to the cholesterol-lowering effect of HMG-CoA reductase inhibitors in type 2 diabetic subjects. (2010)
  • Author(s): T. Takahashi, K. Takahashi, M. Yamashina, C. Maesawa, T. Kajiwara, H. Taneichi, N. Takebe, Y. Kaneko, T. Masuda, J. Satoh
  • Journal Title: Diabetes Care 33 Pages: 463-466
• [Journal Article] Expression profiles of nestin in vascular smooth muscle cells in vivo and in vitro. (2010)
  • Author(s): H. Oikawa, K. Hayashi, C. Maesawa, T. Masuda, K. Sobue
  • Journal Title: Exp Cell Res 316 Pages: 940-950
• [Journal Article] Immunohistochemical Study of HER2 and TUBB3 Proteins in Extramammary Paget Disease. (2010)
  • Author(s): A. Miyamoto, K. Akasaka, H. Oikawa, T. Akasaka, T. Masuda, C. Maesawa
  • Journal Title: Am J Dermatopathol
• [Journal Article] Comparison of the volar locking plate and the bridging external fixator in the treatment of distal radius fracture based on range of wrist motion assessed by functional radiography. (2010)
  • Author(s): Sato K
  • Journal Title: Med Sci Monit. Volume: 16 Pages: 207-212
  • Peer Reviewed
• [Journal Article] Dedifferentiated liposarcoma of the retroperitoneum with osteosarcomatous component: report of two cases. (2009)
  • Author(s): Toshiyasu, S. Ehara, T. Yamaguchi, J. Nishida, H. Shiraishi
  • Journal Title: Clin Imaging 33 Pages: 70-74
• [Journal Article] Enhanced goblet cell hyperplasia in HDC knockout mice with allergic airway inflammation. (2009)
  • Author(s): K. Yamauchi, H.M. Piao, T. Nakadate, T. Shikanai, Y. Nakamura, H. Ito, T. Mouri, H. Kobayashi, C. Maesawa, T. Sawai, H. Ohtsu, H. Inoue
  • Journal Title: Allergol Int 58 Pages: 125-134
  • NAID: 10025109331
• [Journal Article] Spontaneous [Ca2+]i oscillations in G1/S phase-synchronized cells. (2009)
  • Author(s): A.D. Russa, C. Maesawa, Y. Satoh
  • Journal Title: J Electron Microsc (Tokyo) 58 Pages: 321-329
• [Journal Article] Ontogeny of reticular framework of white pulp and marginal zone in human spleen : immunohistochemical studies of fetal spleens from the 17th to 40th week of gestation. (2009)
  • Author(s): T. Satoh, E. Sakurai, H. Tada, T. Masuda
  • Journal Title: Cell Tissue Res 336 Pages: 287-297
• [Journal Article] Differential microRNA expression between bone marrow side population cells and hepatocytes in adult mice. (2009)
  • Author(s): Y. Nagata, C. Maesawa, H. Tada, Y. Takikawa, A. Yashima-Abo, T. Masuda
  • 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): Y. Minami, M. Satoh, C. Maesawa, Y. Takahashi, T. Tabuchi, T. Itoh, Nakamura
  • Journal Title: Eur J Clin Invest 39 Pages: 359-367
• [Journal Article] DNA hypomethylation at the CpG island is involved in aberrant expression of the L1 cell adhesion molecule gene in colorectal cancer. (2009)
  • Author(s): K. Kato, C. Maesawa, T. Itabashi, K. Fujisawa, K. Otsuka, S. Kanno, H. Tada, Y. Tatemichi, K. Kotani, H. Oikawa, T. Sugai, G. Wakabayashi, T. Masuda
  • Journal Title: Int J Oncol 35 Pages: 467-476
• [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): K. Akasaka, C. Maesawa, M. Shibazaki, F. Maeda, K. Takahashi, T. Akasaka, T. Masuda
  • Journal Title: J Invest Dermatol 129 Pages: 1516-1526
• [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
  • Peer Reviewed
• [Journal Article] Clinical findings of hibernoma of the buttock and thigh : rare involvements and extremely high uptake of FDG-PET (2009)
  • Author(s): Nishida J, Ehara S, Shiraishi H, Tada H, Satoh T, Okada K, Shimamura T.
  • Journal Title: Med Sci Monit 15 Pages: 117-122
  • Peer Reviewed
• [Journal Article] Ontogeny of reticular framework of white pulp and marginal zone in human spleen : immunohistochemical studies of fetal spleens from the 17th to 40th week of gestation. (2009)
  • Author(s): Satoh T, Sakurai E, Tada H, Masuda T
  • Journal Title: Cell Tissue Res 336 Pages: 287-297
  • Peer Reviewed
• [Journal Article] Down-regulation of microRNA-127 is associated with overexpression of BCL6 protein in osteosarcoma cells. (2009)
  • Author(s): Masuda S, Maeasawa C, Nishida J, Satoh T, et al.
  • Journal Title: Cancer Sci 100(In press)
  • 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): S. Mitomo, C. Maesawa, S. Ogasawara, T. Iwaya, M. Shibazaki, A. Yashima-Abo, K. Kotani, H. Oikawa, E. Sakurai, N. Izutsu, K. Kato, H. Komatsu, K. Ikeda, G. Wakabayashi, T. Masuda
  • Journal Title: Cancer Sci 99 Pages: 280-286
  • NAID: 10024002213
• [Journal Article] Epigenetic modification is involved in aberrant expression of class III beta-tubulin, TUBB3, in ovarian cancer cells. (2008)
  • Author(s): N. Izutsu, C. Maesawa, M. Shibazaki, H. Oikawa, T. Shoji, T. Sugiyama, T. Masuda
  • Journal Title: Int J Oncol 32 Pages: 1227-1235
• [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): H. Itabashi, C. Maesawa, H. Oikawa, K. Kotani, E. Sakurai, K. Kato, H. Komatsu, H. Nitta, H. Kawamura, G. Wakabayashi, T. Masuda
  • Journal Title: Hepatol Res 38 Pages: 601-613
  • NAID: 10024148920
• [Remarks] ホームページ等