Downregulation of miR-200a-3p, Targeting CtBP2 Complex, Is Involved in the Hypoproduction of IL-2 in Systemic Lupus Erythematosus-Derived T Cells.
| Project/Area Number |
16K19602
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Collagenous pathology/Allergology
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| Research Institution | Okayama University |
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Principal Investigator |
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| Project Period (FY) |
2016-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 全身性エリテマトーデス / エピジェネティクス / microRNA / インターロイキン２ / miR-200a-3p / ＺＥＢ１ / ＺＥＢ２ / ＣｔＢＰ２ / インターロイキン2 / ZEB1 / ZEB2 / CtBP2 / 膠原病学 |
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| Outline of Final Research Achievements |
To identify candidate disease-related microRNAs, we performed RNA sequencing and focused on miR-200a-3p which was significantly decreased, whereas its putative targets, ZEB2 and CtBP2, were upregulated in CD4+ T cells from lupus prone mice compared with the control. The complex of ZEB1/2 is known to suppress various genes including IL-2 by recruiting CtBP2. Therefore, we hypothesized that decreased miR-200a-3p causes IL-2 deficit through the ZEB/CtBP2 complex in SLE CD4+ T cells. Overexpression of miR-200a-3p suppressed the expression of these complexes and these bindings to IL-2 promoter region which caused IL-2 overexpression in EL4 cells. In addition, the ZEB1/CtBP2 complex on the region was significantly increased in stimulated lupus CD4+ T cells. Our studies have revealed a new epigenetic pathway in the control of IL-2 production in SLE whereby low levels of miR-200a-3p accumulate the binding of the ZEB1/CtBP2 complex to the IL-2 promoter and suppress IL-2 production.
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Report
(3 results)
Research Products
(3 results)
