Relationship of endometriosis with methylation status in the homeobox A10 promoter region and its protein expression
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Endometriosis patients showed HOXA10 promoter hypermethylation and decreased HOXA10 protein expression in endometrial tissues, with expression negatively correlated to methylation status.
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Abstract
Objective DNA methylation in the pathogenesis of endometriosis is drawing more and more attention from the medical world.This study aimed to evaluate the methylation status of the Homeobox-A10 (HOXA10) gene promoter region and the expression of the HOXA10 protein in endometriosis,and to explore the relationship of endometriosis with the aberrant methylation and expression of HOXA10 and its clinical significance.Methods The methylation-specific PCR(MSP) and the immunohistochemical SP methods were employed to detect both the methylation status of the HOXA10 promoter and its expression in the eutopic and ectopic endometrial tissues from 36 endometriosis patients,with normal endometrial tissue samples from 12 healthy women as controls.Results Hypermethylation of the HOXA10 promoter region was present in 38.9% (14/36) of the ectopic endometrial tissue samples and 25.0% (9/36) of the eutopic endometrial tissue samples,all in endometriosis of stages Ⅲ and Ⅳ,but no hypermethylation was found in the endometrial tissues of the normal controls,with significant differences between the two groups (P0.05).The ectopic and eutopic endometria from the endometriosis patients failed to show similar up-regulation of the HOXA10 expression as demonstrated in the controls (P0.05).Moreover,decreased expression of HOXA10 was observed in the nuclei of stomal cells in the ectopic endometrium,with significant differences from the control samples (P0.05).The expression level of the HOXA10 protein was negatively correlated with the methylation status of the HOXA10 gene promoter region in the ectopic endometrium (rs=-0.368).Conclusion The aberrant methylation of the HOXA10 promoter region may result in the down-regulation of the gene expression in the endometrium of endometriosis women,which plays an important role in the progression of endometriosis.
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