PDF(Pubmed)
Abstract：
This study explores the role of circadian clock genes in the progression of astrocytic tumors, a prevalent type of brain tumor. The aim was to assess the expression patterns of these genes in relation to the tumor grade. Using microarray analysis, qRT-PCR, and methylation-specific PCR, we examined gene expression, DNA methylation patterns, and microRNA interactions in tumor samples from 60 patients. Our results indicate that the expression of key circadian clock genes, such as clock circadian regulator (CLOCK), protein kinase AMP-activated catalytic subunit alpha 1 (PRKAA1), protein kinase AMP-activated catalytic subunit alpha 2 (PRKAA2), protein kinase AMP-activated non-catalytic subunit beta 1 (PRKAB1), protein kinase AMP-activated non-catalytic subunit beta 2 (PRKAB2), period circadian regulator 1 (PER1), period circadian regulator 2 (PER2) and period circadian regulator 3 (PER3), varies significantly with the tumor grade. Notably, increased CLOCK gene expression and protein levels were observed in higher-grade tumors. DNA methylation analysis revealed that the promoter regions of PER1-3 genes were consistently methylated, suggesting a mechanism for their reduced expression. Our findings also underscore the complex regulatory mechanisms involving miRNAs, such as hsa-miR-106-5p, hsa-miR-20b-5p, and hsa-miR-30d-3p, which impact the expression of circadian clock-related genes. This underscores the importance of circadian clock genes in astrocytic tumor progression and highlights their potential as biomarkers and therapeutic targets. Further research is needed to validate these results and explore their clinical implications.
摘要：
本研究探讨生物钟基因在星形细胞肿瘤进展中的作用,一种常见的脑肿瘤.目的是评估这些基因与肿瘤等级相关的表达模式。使用微阵列分析，qRT-PCR,和甲基化特异性PCR，我们检查了基因表达，DNA甲基化模式，60例患者肿瘤样本中的microRNA相互作用。我们的结果表明，关键的生物钟基因的表达，如时钟昼夜节律调节器(CLOCK)，蛋白激酶AMP激活的催化亚基α1（PRKAA1），蛋白激酶AMP激活的催化亚基α2（PRKAA2），蛋白激酶AMP激活的非催化亚基β1（PRKAB1），蛋白激酶AMP激活的非催化亚基β2（PRKAB2），周期昼夜节律调节器1(PER1)，周期昼夜节律调节器2(PER2)和周期昼夜节律调节器3(PER3)，肿瘤分级有显著差异。值得注意的是,在高级别肿瘤中观察到CLOCK基因表达和蛋白质水平升高.DNA甲基化分析显示PER1-3基因的启动子区域一致甲基化,表明了它们表达降低的机制。我们的发现还强调了涉及miRNAs的复杂调控机制，如hsa-miR-106-5p，hsa-miR-20b-5p,和hsa-miR-30d-3p,影响生物钟相关基因的表达。这强调了生物钟基因在星形细胞肿瘤进展中的重要性，并强调了它们作为生物标志物和治疗靶标的潜力。需要进一步的研究来验证这些结果并探索其临床意义。
