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Compound 12 exerted significant activity against HDAC enzyme and inhibited HDAC4 and 5 in nM concentrations.
In brief, it has been demonstrated that epigenetic factors, such as hypermethylation in HDAC4, HDAC5, and HDAC6 gene promoters, down-regulation in miR424/ 503, up-regulation of miR21, miR143, miR210, miR27a, and miR130/301, and upregulation of ion channels could display a potential function in molecular pathways alterations implicated in endothelial dysfunction in PAH (90).
 In addition to regulating various cellular processes, miRNAs are epigenetic modulators by targeting mRNAs of epigenetic regulators including DNA methyltransferase 3 alpha (DNMT3A), DNA methyltransferase 3 Beta (DNMT3B), polycomb mRNAs, EZH2 (as shown above), BMI1 and HDAC4. [62,63] miR-122 is most abundant in the liver and is frequently downregulated in HCC, which suggests its role as a tumour suppressor.
miR-1 and miR-206 downregulate histone deacetylase 4 (HDAC4).
Similarly, miR-29a regulates HDAC4 expression, displaying protective effects from glucocorticoid-induced bone loss by modulating [beta]-catenin accumulation and OB differentiation .
The CDKL5 substrates that have, so far, been identified are MeCP2 [11, 12], DNA methyltransferase 1 (DNMT1) , Rac1 , amphiphysin 1 , PSD-95 , NGL-1 , Mind Bomb 1 (Mib1) , Shootin1 , HDAC4 , and IQGAP1 .
Wen et al., "Overexpressed HDAC4 is associated with poor survival and promotes tumor progression in esophageal carcinoma," Aging, vol.
Gene Therapy to Activate HDAC4 for Retinitis Pigmentosa - Drug Profile 74
Se identificaron 47 proteinas expresadas diferencialmente, de las cuales, la trombospondina 1 (TSP1) aumento su expresion, mientras que la enzima histona deacetilasa 4 (HDAC4) presento una reduccion.
 demonstrated that the injection of leptin into ob/ob mice caused upregulation of circulating norepinephrine, increase of the cAMP content in epididymal fat pads, and HDAC4 dephosphorylation in WAT, triggering anti-inflammatory signals in ATMs.
In glioblastoma, the expression of HDAC1 and HDAC3 is inversely correlated with survival of GB patients, whereas that of HDAC4, HDAC5, HDAC6, and HDAC11 is positively correlated with survival of glioma patients .
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