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Publication : miR-188 promotes senescence of lineage-negative bone marrow cells by targeting MAP3K3 expression.

First Author  Zheng Y Year  2017
Journal  FEBS Lett Volume  591
Issue  15 Pages  2290-2298
PubMed ID  28640956 Mgi Jnum  J:243930
Mgi Id  MGI:5912709 Doi  10.1002/1873-3468.12720
Citation  Zheng Y, et al. (2017) miR-188 promotes senescence of lineage-negative bone marrow cells by targeting MAP3K3 expression. FEBS Lett 591(15):2290-2298
abstractText  Lineage-negative bone marrow cells (lin-BMCs) have reparative potential for overcoming endothelial dysfunction and reducing cardiovascular risk. Here, we found that miR-188 is upregulated and mitogen-activated protein kinase kinase kinase 3 (MAP3K3) is downregulated in aged lin-BMCs, whereas their expression is reversed in young lin-BMCs. We identified and confirmed MAP3K3 as a direct target of miR-188. MiR-188 overexpression or MAP3K3 silencing in young lin-BMCs increases p16 and p21 expression, enhances cell senescence, and decreases the ability for cell proliferation, migration, and tube formation. Conversely, miR-188 suppression in aged lin-BMCs yields the opposite results. We further found that MAP3K3 is involved in miR-188-induced promotion of lin-BMC senescence. All data reveal that miR-188 induces lin-BMC senescence by targeting MAP3K3 expression, thus, providing new theoretical basis for the prevention and treatment of cardiovascular diseases.
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