Significance and Molecular mechanisms of abnormal expression of miRNA in carcinogenesis.

2012 Fiscal Year Final Research Report

• Project/Area Number: 22300318
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Carcinogenesis
• Research Institution: The University of Tokyo
• Principal Investigator: IBA Hideo 東京大学, 医科学研究所, 教授 (60111449)
• Co-Investigator(Kenkyū-buntansha): HARAGUCHI Takeshi 東京大学, 医科学研究所, 助教 (10549455) ; KOHARA Michinori 東京都医学総合研究所, 副参事研究員 (10250218) ; INADA Kenichi 藤田保健衛生大学, 医学部, 准教授 (70246081) ; MIZUTANI Taketoshi 東京大学, 医科学研究所, 助教
• Project Period (FY): 2010 – 2012
• Keywords: 発現制御 / 上皮‐間充織変換 / Cdx1 / miR-200c / miR-199a / miR-15/-16 / Brm

Research Abstract

There have been reported to be about 1000 species of miRNA in human, among them, such miRNAs as miR-21, miR-199a, miR-15/-16 and miR-200c are expressed at aberrant levels in cancer tissues. In this research, we demonstrated how these aberrant expression were induced and maintained, and found in several cases, stable gene regulatory net works have been formed among the miRNA, transcription factors and SWI/SNF chromatin remodeling factors. We further show the RNA decoy molecules that we developed for the inhibitor of specificmicorRNA activity (designated TuD) is very effective for the analysis of molecular mechanisms and for future therapietic application for cancer.

Research Products

• [Journal Article] Multiple microRNAs induced by Cdx1 suppress Cdx2 in human colorectal tumor cells. (2012)
  • Author(s): Tagawa, T., Haraguchi, T., Hiramatsu, H., Kobayashi, K., Sakurai, K., Inada, K., and Iba, H.
  • Journal Title: Biochem. J. Volume: 447 Pages: 449-455
  • Peer Reviewed
• [Journal Article] Extracellular ATP mediates mast cell-dependent intestinal inflammation through P2X7 purinoceptors. (2012)
  • Author(s): Kurashima, Y., Amiya T., Nochi T., FujisawaK., Haraguchi T., Iba H., Tsutsui H., Sato S., Nakajima S., Iijima H., Kubo M., Kunisawa, J., and Kiyono H.
  • Journal Title: Nature Communications. Volume: 3 Pages: 1034
  • DOI: doi:10.1038/ncomms2023
  • Peer Reviewed
• [Journal Article] Double plant homeodomain (PHD) finger proteins DPF3a and -3b are required as transcriptional co-activators in SWI/SNF complex-dependent activation of NF- RelA/p50 heterodimer. (2012)
  • Author(s): Ishizaka, A., Mizutani, T., Kobayashi, K., Tando, T., Sakurai, K., Fujiwara, T., and Iba, H.
  • Journal Title: J. Biol. Chem. Volume: 287 Pages: 11924-11933
  • Peer Reviewed
• [Journal Article] A potent2'-O-methylated RNA-based microRNAinhibitor with unique secondary structures. (2012)
  • Author(s): Haraguchi, T., Nakano, H., Tagawa, T., Ohki, T., Ueno, Y., Yoshida, T., and Iba, H.
  • Journal Title: Nucleic Acids Res. Volume: 40 Pages: e58
  • Peer Reviewed
• [Journal Article] MicroRNA regulation of glycoprotein B5R in oncolytic vaccinia virus reduces viral pathogenicity without impairing its antitumor efficacy. (2011)
  • Author(s): Hikichi, M., Kidokoro, M., Haraguchi,T., Iba, H., Shida, H., Tahara, H., and Nakamura, T.
  • Journal Title: Molecular Therapy
  • DOI: doi:10.1038
  • Peer Reviewed
• [Journal Article] microRNAs miR-199a-5p and -3p target the Brm subunit of SWI/SNFto generate a double-negative feedback loop ina variety of human cancers. (2011)
  • Author(s): Sakurai, K., Furukawa, C., Haraguchi, T., Inada, K.,Shiogama, K., Tagawa, T., Fujita, S., Ueno, Y., Ogata, A., Ito,M., Tsutsumi, Y., and Iba, H.
  • Journal Title: Cancer Research Volume: 71 Pages: 1680-1689
  • Peer Reviewed
• [Journal Article] Incorporation of biaryl units into the 5′ and3′ ends of sense and antisense strands of siRNA duplexes improves strand selectivity and nuclease resistance. (2011)
  • Author(s): Yoshikawa, K., Ogata, A., Matsuda, C., Kohara, M., Iba, H., Kitade, Y., and Ueno, Y.
  • Journal Title: Bioconjug. Chem. Volume: 22 Pages: 42-49
  • Peer Reviewed
• [Journal Article] Biarylmodification of the 5'-terminus of one strandof a microRNA duplex induces strand specificity. (2010)
  • Author(s): Ogata, A., Furukawa, C., Sakurai, K., Iba, H., Kitade, Y., and Ueno, Y.
  • Journal Title: Bioorg. Med. Chem. Lett. Volume: 20 Pages: 7299-7302
  • Peer Reviewed
• [Journal Article] Requiem protein links RelB/p52 and theBrm-type SWI/SNF complex in a non-canonical NFκB pathway. (2010)
  • Author(s): Tando, T., Ishizaka, A., Watanabe, H., Ito, T., Iida, S., Haraguchi, T., Mizutani, T., Izumi, T., Isobe, T., Akiyama, T., Inoue, J., and Iba, H.
  • Journal Title: J. Biol. Chem. Volume: 285 Pages: 21951-21960
  • Peer Reviewed
• [Presentation] Molecular switches formed by miR-199a and Brm, a catalytic subunit of SWI/SNF chromatin remodeling factor,determine inflammation status in cancer cells. (2012)
  • Author(s): Iba, H.
  • Organizer: Innate Immunity Society (IEIIS) meeting
  • Place of Presentation: 東京
  • Year and Date: 2012-10-25
• [Presentation] Identification of essential factors of SWI/SNF dependent-NF-kappaB activation and their roles in carcinogenesis. (2012)
  • Author(s): Kobayashi, K., Sakurai, K., Haraguchi, T., Iba, H.
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌
  • Year and Date: 2012-09-20
• [Presentation] SWI/SNFcomplex catalytic subunit, Brm, as a key epigenetical regulatorin cancer cells. (2012)
  • Author(s): Iba, H. et al.
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌
  • Year and Date: 2012-09-19
• [Presentation] Two methods for microRNA inhibition-TuD RNA expression vector & 2'-O-methylated RNA-based microRNA inhibitor, S-TuD. (2012)
  • Author(s): Haraguchi, T., and Iba, H.
  • Organizer: The 10thStem Cell Research Symposium
  • Place of Presentation: 淡路
  • Year and Date: 2012-06-01
• [Presentation] Development of S-TuD, a novel 2'-O-methylated RNA based microRNA inhibitor with unique secondary structures. (2011)
  • Author(s): 原口健 、中野春男、吉田哲郎、 伊庭英夫 :
  • Organizer: 第34回日本分子生物学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 20111213-1216
• [Presentation] A potent2'-O-Methylated RNA based microRNA inhibitor with unique secondary structures. (2011)
  • Author(s): 原口健、中野春男、吉田哲郎、 伊庭英夫
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 20111003-1005
• [Presentation] miRNA as an epigenetic switch. The 18thEast Asia Joint Symposium on Biomedical Research ( (2011)
  • Author(s): Iba, H.
  • Organizer: 第18回東アジアシンポジウム)
  • Place of Presentation: Shanghai
  • Year and Date: 2011-12-08
• [Presentation] HIV-1 promoter is negatively regulated by hnRNPA1 in Tat independent mannor. (2011)
  • Author(s): Mizutani, T., Ishizaka, A., and Iba, H.
  • Organizer: 日本ウイルス学会学術集会(IUMS Sapporo)
  • Place of Presentation: 札幌
  • Year and Date: 2011-09-11
• [Presentation] Development and application ofTough Decoy (TuD) RNAs, which achieve strong and long-term suppression of specific microRNA activity. (2011)
  • Author(s): 伊庭 英夫
  • Organizer: IBC's 3rdAnnual Asia TIDES
  • Place of Presentation: 東京
  • Year and Date: 2011-03-03
• [Presentation] Cancer epigenetics and miRNA (癌のエピジェネティクスとマイクロ RNA) (2010)
  • Author(s): 伊庭 英夫
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪
  • Year and Date: 2010-09-22
• [Remarks]
  • URL: http://www.ims.u-tokyo.ac.jp/div-host-parasite/Version1.html