43 research outputs found
Deciphering the role of histone modifications in uterine leiomyoma: acetylation of H3K27 regulates the expression of genes involved in proliferation, cell signaling, cell transport, angiogenesis and extracellular matrix formation
Uterine leiomyoma (UL) is a benign tumor arising from myometrium (MM) with a high prevalence and unclear pathology. Histone modifications are altered in tumors, particularly via histone acetylation which is correlated with gene activation. To identify if the acetylation of H3K27 is involved in UL pathogenesis and if its reversion may be a therapeutic option, we performed a prospective study integrating RNA-seq (n = 48) and CHIP-seq for H3K27ac (n = 19) in UL vs MM tissue, together with qRT-PCR of SAHA-treated UL cells (n = 10). CHIP-seq showed lower levels of H3K27ac in UL versus MM (p-value < 2.2 × 10−16). From 922 DEGs found in UL vs. MM (FDR < 0.01), 482 presented H3K27ac. A differential acetylation (FDR < 0.05) was discovered in 82 of these genes (29 hyperacetylated/upregulated, 53 hypoacetylated/downregulated). Hyperacetylation/upregulation of oncogenes (NDP,HOXA13,COL24A1,IGFL3) and hypoacetylation/downregulation of tumor suppressor genes (CD40,GIMAP8,IL15,GPX3,DPT) altered the immune system, the metabolism, TGFβ3 and the Wnt/β-catenin pathway. Functional enrichment analysis revealed deregulation of proliferation, cell signaling, transport, angiogenesis and extracellular matrix. Inhibition of histone deacetylases by SAHA increased expression of hypoacetylated/downregulated genes in UL cells (p < 0.05). Conclusively, H3K27ac regulates genes involved in UL onset and maintenance. Histone deacetylation reversion upregulates the expression of tumor suppressor genes in UL cells, suggesting targeting histone modifications as a therapeutic approach for UL
Effect of the acrylic acid content on the permeability and water uptake of latex films
Acrylic acid (AA) is a monomer commonly employed in emulsion polymerization
to provide electrostatic colloidal stability and improve specific film
performance. The addition of AA not only modifies the kinetics of the
polymerization, but also it takes part in the interaction between colloidal
particles, which has a strong influence on their packing and consequent latex
film properties. In this contribution a theoretical modeling of the latex film
formation is presented and compared to experimental results: water vapor
permeability and latex film capacitance are studied as a function of AA
content. It has been shown that water uptake is mainly affected by film
morphology which in turn is defined by intercolloidal interaction and drying
rate.Comment: 16 pages, 7 figure
Oviposition activity and seasonal pattern of a population of Aedes (Stegomyia) aegypti (L.) (Diptera: Culicidae) in subtropical Argentina
Targeting histone modifications: H3K27 acetylation regulates the expression of genes involved in key processes of uterine leiomyoma pathogenesis
Angiotensin system inhibitors and survival in patients with metastatic renal cell carcinoma treated with VEGF-targeted therapy: A pooled secondary analysis of clinical trials
H3K4me3 mediates uterine leiomyoma pathogenesis via neuronal processes, synapsis components, proliferation, and Wnt/β-catenin and TGF-β pathways
BACKGROUND: Uterine leiomyomas (UL) are the most common benign tumor in women of reproductive age. Their pathology remains unclear, which hampers the development of safe and effective treatments. Raising evidence suggests epigenetics as a main mechanism involved in tumor development. Histone modification is a key component in the epigenetic regulation of gene expression. Specifically, the histone mark H3K4me3, which promotes gene expression, is altered in many tumors. In this study, we aimed to identify if the histone modification H3K4me3 regulates the expression of genes involved in uterine leiomyoma pathogenesis. METHODS: Prospective study integrating RNA-seq (n = 48) and H3K4me3 CHIP-seq (n = 19) data of uterine leiomyomas versus their adjacent myometrium. Differentially expressed genes (FDR  1 or  1 or < - 1) was epigenetically mediated by H3K4me3. Further, 50 genes were differentially trimethylated (FDR < 0.05), including 33 hypertrimethylated/upregulated, and 17 hypotrimethylated/downregulated genes. Functional enrichment analysis of the latter showed dysregulation of neuron-related processes and synapsis-related cellular components in uterine leiomyomas, and a literature review study of these DEG found additional implications with tumorigenesis (i.e. aberrant proliferation, invasion, and dysregulation of Wnt/β-catenin, and TGF-β pathways). Finally, SATB2, DCX, SHOX2, ST8SIA2, CAPN6, and NPTX2 proto-oncogenes were identified among the hypertrimethylated/upregulated DEG, while KRT19, ABCA8, and HOXB4 tumor suppressor genes were identified among hypotrimethylated/downregulated DEG. CONCLUSIONS: H3K4me3 instabilities alter the expression of oncogenes and tumor suppressor genes, inducing aberrant proliferation, and dysregulated Wnt/β-catenin, and TGF-β pathways, that ultimately promote uterine leiomyoma progression. The reversal of these histone modifications may be a promising new therapeutic alternative for uterine leiomyoma patients