2013 Fiscal Year Final Research Report
Identification and analysis of functional RNAs regulated by p53 family members in gastrointestinal tumorigenesis
Project/Area Number |
23590920
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Gastroenterology
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Research Institution | Sapporo Medical University |
Principal Investigator |
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Project Period (FY) |
2011 – 2013
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Keywords | p53 / p73 / p63 / 機能性RNA / miRNA / 消化器癌 |
Research Abstract |
The miR-200 family includes two clusters: miR-200b-200a-429 located on chromosome 1; and miR-200c-141 located on chromosome 12. We identified response elements located around both clusters that are responsive to p53 family. Here, in silico miRNA target prediction identified the v-crk sarcoma virus CT10 oncogene homolog-like (CRKL) as a potential miR-200b/200c/429 target. MiR-200b/200c/429 inhibits the expression of CRKL by directly targeting its 3'-UTR region. Importantly, CRKL expression was decreased in cancer cells with introduction of wild-type p53 and TAp63. Oncomine database shows that CRKL levels are significantly overexpressed in multiple cancer types compared with the corresponding normal tissues. We also found that CRKL was overexpressed in primary breast cancer tissues harboring mutant p53 genes. Our results indicate that a p53-inducible miRNA, 200b/200c/429 is a negative regulator of the CRKL oncoprotein and suggest a new p53-miR-200-CRKL pathway in carcinogenesis.
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Author(s)
Ito M, Mitsuhashi K, Igarashi H, Nosho K, Naito T, Yoshii S, Takahashi H, Fujita M, Sukawa Y, Yamamoto E, Takahashi T, Adachi Y, Nojima M, Sasaki Y, Tokino T, Baba Y, Maruyama R, Suzuki H, Imai K, Yamamoto H, Shinomura Y
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Int J Cancer
Volume: (in press)
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Adachi Y, Ohashi H, Imsumran A, Yamamoto H, Matsunaga Y, Taniguchi H, Nosho K, Suzuki H, Sasaki Y, Arimura Y, Carbone DP, Imai K, Shinomura Y
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Tumour Biol
Volume: 35
Pages: 973-985
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Kashima L, Idogawa M, Mita H, Shitashige M, Yamada T, Ogi K, Suzuki H, Toyota M, Ariga H, Sasaki Y, Tokino T
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Journal Title
J Biol Chem
Volume: 287
Pages: 12975-84
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[Journal Article] Heat shock enhances the expression of cytotoxic granule proteins and augments the activities of tumor-associated antigen-specific cytotoxic T lymphocytes2012
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Takahashi A, Torigoe T, Tamura Y, Kanaseki T, Tsukahara T, Sasaki Y, Kameshima H, Tsuruma T, Hirata K, Tokino T, Hirohashi Y, Sato N
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Journal Title
Cell Str ess Chaperones
Volume: 17
Pages: 757-63
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[Journal Article] CLCA2, a target of the p53 family, negatively regulates cancer cell migration and invasion2012
Author(s)
Sasaki Y, Koyama R, Maruyama R, Hirano T, Tamura M, Sugisaka J, Suzuki H, Idogawa M, Shinomura Y, Tokino T
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Journal Title
Cancer Biol Ther
Volume: 13
Pages: 1512-21
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[Journal Article] Molecular Dissection of Premalignant Colorectal Lesions Reveals Early Onset of the CpG Island Methylator Phenotype2012
Author(s)
Yamamoto E, Suzuki H, Yamano HO, Maruyama R, Nojima M, Kamimae S, Sawada T, Ashida M, Yoshikawa K, Kimura T, Takagi R, Harada T, Suzuki R, Sato A, Kai M, Sasaki Y, Tokino T, Sugai T, Imai K, Shinomura Y, Toyota M
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Journal Title
Am J Pathol
Volume: 181
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[Journal Article] Myogenic lineage differentiated mesenchymal stem cells enhance recovery from dextran sulfate sodium-induced colitis in the rat2011
Author(s)
Tanaka H, Arimura Y, Yabana T, Goto A, Hosokawa M, Nagaishi K, Yamashita K, Yamamoto H, Sasaki Y, Fujimiya M, Imai K, Shinomura Y
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Journal Title
J Gastr oenter ol
Volume: 46
Pages: 143-152
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Peer Reviewed
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[Journal Article] Epigenetic alteration of DNA in mucosal wash fluid predicts invasiveness of colorectal tumors2011
Author(s)
Kamimae S, Yamamoto E, Yamano H, Nojima M, Suzuki H, Ashida M, Hatahira T, Sato A, Kimura T, Yoshikawa K, Harada T, Hayashi S, Takamaru H, Maruyama R, Kai M, Nishiwaki M, Sugai T, Sasaki Y, Tokino T, Shinomura Y, Imai K, Toyota M
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Journal Title
Cancer Prev Res
Volume: 4
Pages: 674-83
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Peer Reviewed
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[Journal Article] Genome-wide profiling of chromatin signatures reveals epigenetic regulation of MicroRNA genes in colorectal cancer2011
Author(s)
Suzuki H, Takatsuka S, Akashi H, Yamamoto E, Nojima M, Maruyama R, Kai M, Yamano HO, Sasaki Y, Tokino T, Shinomura Y, Imai K, Toyota M
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Journal Title
Cancer Res
Volume: 71
Pages: 5646–58
DOI
Peer Reviewed
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[Journal Article] p53 negatively regulates the hepatoma growth factor HDGF2011
Author(s)
Sasaki Y, Negishi H, Idogawa M, Yokota I, Koyama R, Kusano M, Suzuki H, Fujita M, Maruyama R, Toyota M, Saito T, Tokino T
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Journal Title
Cancer Res
Volume: 71
Pages: 7038-47
DOI
Peer Reviewed
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[Presentation] CLCA2, a target of the p53 family, negatively regulates cancer cell migration and invasion2013
Author(s)
Sasaki Y, Koyama R, Maruyama R, Tamura M, Ohashi T, Idogawa M, Suzuki H, Shinomura Y, Tokino T
Organizer
9th AACR-JCA Joint International Conference
Place of Presentation
Maui, Hawaii
Year and Date
2013-02-24
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