| 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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| Co-Investigator(Kenkyū-buntansha) |
森 一憲 昭和大学, 薬学部, 助教 (60349040)
石川 文博 昭和大学, 薬学部, 助教 (60515667)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | ミトコンドリアDNA / HMGA2 / ミトコンドリアDNA変異 / 肝細胞がん / ミトコンドリア呼吸鎖活性 / ミトコンドリア / E2F1 |
|---|
| 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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