2013 Fiscal Year Final Research Report
Mechanism of senescence-associated microRNA inhibiting cell growth and metastasis
| Project/Area Number |
23300363
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Clinical oncology
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| Research Institution | Hiroshima University |
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Principal Investigator |
TAHARA Hidetoshi 広島大学, 大学院医歯薬保健学研究院, 教授 (00271065)
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| Co-Investigator(Kenkyū-buntansha) |
OCHIYA Takahiro 国立がん研究センター研究所, 分子細胞治療研究分野, 分野長 (60192530)
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| Project Period (FY) |
2011-04-01 – 2014-03-31
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| Keywords | 細胞老化 / がん / マイクロRNA / 核酸医薬 |
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| Research Abstract |
We identified that senescent associated miRNA, SA-miRNA, miR-22 is down-regulated in various cancer cell lines including MCF-7, MDA-MB-231 and SiHa cells, suggesting that miR-22 should play important roles for cancer progression. Transfection of miR-22 strongly induces cellular senescence accompanied by enlarged morphology, senescent-associated b-Gal activity (SA-b-Gal) and senescent associated heterochromatin foci (SAHF) formation. By using 3-UTR luciferase assay and Western analysis, we identified CDK6, SP-1, SIRT1 and Histone H3.3 are targets of miR-22. Furthermore, synthetic miR-22 delivery significantly suppresses tumor growth and metastasis in vivo in a murine breast metastasis cancer model using MDA-MB-231 Luc cell lines. Our study provides the first evidence that the senescence-associated miRNA induces cellular senescence in human fibroblasts and cancer cells, and acts as tumor suppressor to play an important role in tumorigenesis.
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