Although serum bile acid concentrations are approximately 10 mM in healthy subjects, the crosstalk between the biliary system and vascular repair has never been investigated. In this study, tauroursodeoxycholic acid (TUDCA) induced dissociation of CD34 1 hematopoietic stem cells (HSCs) from stromal cells by reducing adhesion molecule expression. TUDCA increased CD341 /Sca1 1 progenitors in mice peripheral blood (PB), and CD34
1, CD31
ZNF224 is a Krüppel-associated box-containing zinc-finger protein which represses gene transcription by interacting with various co-repressors. However, its consensus DNA sequences and target genes are not fully identified. In this study, we identified and characterized consensus DNA sequences containing 5′-CAGC-3′; recognized by ZNF224 through ChIP-sequencing, which further confirmed by ELISA, SPR, qPCR, and luciferase activity assay. ZNF224 increased miR-663a transcription by binding to miR-663a promoter, which in turn binds to 3′; UTR of p53 and p21 to decrease their expression. miR-663a antagonist abolished ZNF224-mediated suppression of p21 and p53, resulting in the enhanced apoptosis by CPT. The analyses using human breast ductal carcinoma tissues exhibited that the expression of ZNF224 and miR-663a was increased in cancer compared to non-cancer region. Consequently, ZNF224 increases cell survival and decreases apoptosis by decreasing the expression of p53 and p21 via miR-663a as a transcriptional activator. Taken together, we identified and characterized DNA binding element of ZNF224, and its target genes, miR-663a, which provides a novel insight in the down-regulation of p21 and p53 via miR-663a by ZNF224 in breast cancer.
Background:The increase of PPAR␥ stability could contribute to lower blood glucose levels. Results: PPAR␥ stability is increased by the deubiquitinating activity of HAUSP. Conclusion: HAUSP overexpression could decrease blood glucose and triglyceride levels at least in part by deubiquitinating and stabilizing PPAR␥ in the liver. Significance: Identification of a novel enzyme (HAUSP) that deubiquitinates and stabilizes PPAR␥ and its potential role in liver glucose and lipid metabolism are significant.
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