Induction of endometoriotic cells by the master regulatory genes detected with gene regulatory network analysis
| Project/Area Number |
16K11142
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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 |
Obstetrics and gynecology
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| Research Institution | Yamaguchi University |
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Principal Investigator |
MAEKAWA Ryo 山口大学, 医学部附属病院, 講師 (90598749)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 子宮内膜症 / マスター遺伝子 / 卵巣チョコレート嚢腫 / マスターレギュレータ遺伝子 / マスターレギュレータ / HOXC8 / Endometriosis / PPAR gamma / ESR1 / TGF beta / TNF alpha / driver gene / master gene / 遺伝子発現 / DNAメチル化 |
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| Outline of Final Research Achievements |
To find the candidate genes of upstream regulatory gene in ovarian endometrioma, we performed SMITE analysis. We focused on HOCX8 as a candidate gene of upstream regulatory gene. To clarify the function of HOXC8, HOXC8-overexpressing cells were established using human endometrial stromal cells. The expression statuses of 582 genes were altered by HOXC8-overexpression. Gene Ontology analysis in these genes revealed that genes associated with cell proliferation, adhesion and composition of extracellular matrix were increased. KEGG pathway analysis indicated nine intracellular signaling pathways were altered. It is known that activation of TGFβ-pathway is characteristic of ovarian endometrioma, and is involved in the cell proliferation, invasion and adhesion. In the functional analysis, cell proliferation, migration and adhesion activities were enhanced in the HOXC8-overexpressing cells. HOXC8 is considered to be an upstream regulatory gene in ovarian endometrioma.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究により、極めて発症頻度の高い子宮内膜症の病態に関与する重要な遺伝子が明らかとなった。このような疾患のマスター遺伝子を同定することは、将来的な治療標的になる可能性があり、本研究が与える学術的意義は大きいと考えられる。
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Report
(4 results)
Research Products
(15 results)
