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Aberrant Histone Modification Patterns And Serum MicroRNA Expression In Endometriosis

Posted on:2013-12-20Degree:DoctorType:Dissertation
Country:ChinaCandidate:X M XiaFull Text:PDF
GTID:1264330401979095Subject:Obstetrics and gynecology
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Part â…  Aberrant histone acetylation and methylation levels in endometriosisObjective To investigate the alterations in histone modifications in woman with endometriosis.Methods Global histone H3/H4acetylation and H3K4/H3K9methylation in eutopic and ectopic endometrium from15endometriosis patients were assayed using the EpiQuikTM global histone H3/H4acetylation and H3K4/H3K9methylation assay kits. Quantitative real-time RT-PCR (reverse transcriptase-polymerase chain reaction) was applied to measure mRNA levels of12members of histone related chromatin modifier genes.Results Histone H4hypoacetylation was detected both in eutopic and ectopic endometrium. There were no difference between patients with endometriosis and controls on global levels of H3acetylation. Furthermore, global histone H3K4hypomethylation and H3K9hypomethylation were detected both in ectopic and eutopic endometrium (p=0.000), and in ectopic endometrium (p=0.000), respectively. SIRT1mRNA level was significantly decreased in eutopic endometrium, while mRNA levels of HDAC1, SUV39H1, SUV39H2and G9a were significantly downregulated in ectopic endometrium. HDAC2mRNA level was significantly increased in eutopic endometrium. PCAF mRNA level was significantly increased in ectopic endometrium.Conclusions Global histone acetylation and methylation were decreased and the expression levels of histone acetyltransferases, histone deacetylases and histone methyltransferases were aberrant in endometriosis, suggesting their possible involvement in the pathogenesis of endometriosis. Part â…¡ Abnormal microRNA expression in serum from patients with endometriosisObjective To investigate the alterations of microRNA (miRNA) in serum from patient with endometriosis.Methods Serum from9patients with endometriosis and9normal controls were extracted. Total RNA including miRNAs was extracted using Trizol reagent. MiRNAs with differential expression were detected by high-throughput miRNA sequencing method and the results were confirmed in30patients with endometriosis and20healthy controls by Real-time PCR.Results The results showed that98miRNAs expression was downregulated and10miRNAs expression was significantly upregulated in serum from patients with endometriosis compared to normal controls. Downregulated molecules of miRNAs (hsa-miR-99b-5p, hsa-miR-127-3p, hsa-miR-30c-5p) and upregulated molecules of miRNAs (hsa-miR-424-3p and hsa-miR-185-5p) were seleted to confirmed in30patients and20healthy controls by Real-time PCR. Hsa-miR-99b-5p, hsa-miR-127-3p and hsa-miR-30c-5p expression level was significantly reduced, whereas hsa-miR-424-3p and hsa-miR-185-5p expression level were significantly upregulated in serum from endometriosis patients (p<0.05) Conclusions Aberrant miRNA expression may play a role in the pathogenesis of endometriosis.
Keywords/Search Tags:histone, endometriosis, acetylation, methylation, post-translational modificationendometriosis, microRNA, serum
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