Fialkova Veronika, Vidomanova Eva, Balharek Tomas, Marcinek Juraj, Kudela Erik, Hanysova Sandra, Visnovsky Jozef, Dobrota Dusan, Hatok Jozef
Department of Medical Biochemistry, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin, Slovakia.
Gen Physiol Biophys. 2017 Dec;36(5):521-529. doi: 10.4149/gpb_2017032.
DNA methylation is a significant epigenetic modification which plays a key role in regulation of gene expression and influences functional changes in endometrial tissue. Aberrant DNA methylation changes result in deregulation of important apoptotic proteins during endometrial carcinogenesis and apoptosis resistance development. Evading apoptosis is still a major problem in the successful treatment of endometrial cancer patients. The aim of our study was to examine the promoter DNA methylation changes in 22 apoptosis-associated genes in endometrioid endometrial cancer patients, precancerous lesions and healthy tissue from various normal menstrual cycle phases using a unique pre-designed methylation platform. We observed as the first a significant difference in promoter DNA methylation status in genes: BCL2L11 (p < 0.001), CIDEB (p < 0.03) and GADD45A (p < 0.05) during endometrial carcinogenesis and BIK gene (p < 0.03) in different phases of normal menstrual cycle. The results of our study indicate that deregulation of mitochondrial apoptotic pathway can considerably contributes to the apoptosis resistance development and may be helpful in identifying of new potent biomarkers in endometrial cancer.
DNA甲基化是一种重要的表观遗传修饰，在基因表达调控中起关键作用，并影响子宫内膜组织的功能变化。异常的DNA甲基化变化导致子宫内膜癌发生和凋亡抵抗发展过程中重要凋亡蛋白的失调。逃避凋亡仍然是成功治疗子宫内膜癌患者的一个主要问题。我们研究的目的是使用独特的预先设计的甲基化平台，检测子宫内膜样子宫内膜癌患者、癌前病变以及来自不同正常月经周期阶段的健康组织中22个凋亡相关基因的启动子DNA甲基化变化。我们首次观察到，在子宫内膜癌发生过程中，基因BCL2L11（p < 0.001）、CIDEB（p < 0.03）和GADD45A（p < 0.05）的启动子DNA甲基化状态存在显著差异，在正常月经周期的不同阶段，BIK基因（p < 0.03）也存在显著差异。我们的研究结果表明，线粒体凋亡途径的失调可能在很大程度上导致凋亡抵抗的发展，并且可能有助于识别子宫内膜癌新的有效生物标志物。
Zotero 插件