2016 Fiscal Year Final Research Report
Significance of mitochondrial DNA mutations in cancer cells: induction of HMGA2 in response to DNA damage
| Project/Area Number |
26460399
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Pathological medical chemistry
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| Research Institution | Showa University |
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Principal Investigator |
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Keywords | ミトコンドリアDNA / HMGA2 |
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| Outline of Final Research Achievements |
In most human cancers, mutations have been identified in mitochondrial DNA (mtDNA). Interestingly, HMGA2, an oncofetal transcriptional regulator, was upregulated in mtDNA replication/transcription (mtR/T)-deficient conditions.
mtR/T deficiency generally causes deterioration in cell growth. In this study, we report that HMGA2 operates to overcome such cell growth defects and promotes EMT. HMGA2 knockdown significantly decreased growth rate and colony forming ability in hepatocellular carcinoma (HCC) cell lines with low mtR/T activities. In parallel, cell-cycle regulators such as cyclin E and E2F2 were downregulated, concomitantly with an increase in SA-ｂ-galactosidase activity. Conversely, the hepatocyte nuclear factor HNF-4a, which suppresses EMT regulators such as SIP, was upregulated. Thus, a novel bifacial role of HMGA2 has emerged in overcoming growth deterioration or senescence induction and promoting EMT, suggesting HMGA2 as a therapeutically promising target for HCC.
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| Free Research Field |
腫瘍細胞生物学
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