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.
本研究探讨了昼夜节律钟基因在星形细胞瘤（一种常见的脑肿瘤）进展中的作用，旨在评估这些基因表达模式与肿瘤分级之间的关系。通过采用微阵列分析、qRT-PCR及甲基化特异性PCR技术，我们对60例患者肿瘤样本中的基因表达、DNA甲基化模式及microRNA相互作用进行了检测。结果显示，关键昼夜节律钟基因——包括时钟昼夜节律调节器（CLOCK）、蛋白激酶AMP激活催化亚基α1（PRKAA1）、蛋白激酶AMP激活催化亚基α2（PRKAA2）、蛋白激酶AMP激活非催化亚基β1（PRKAB1）、蛋白激酶AMP激活非催化亚基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）——的表达水平随肿瘤分级不同而呈现显著差异。值得注意的是，在高级别肿瘤中观察到CLOCK基因表达及蛋白水平升高。DNA甲基化分析显示，PER1-3基因的启动子区域持续存在甲基化，这可能是其表达下调的一种机制。我们的研究结果还强调了涉及microRNA（如hsa-miR-106-5p、hsa-miR-20b-5p和hsa-miR-30d-3p）的复杂调控机制，这些microRNA影响昼夜节律钟相关基因的表达。这凸显了昼夜节律钟基因在星形细胞瘤进展中的重要性，并提示其作为生物标志物和治疗靶点的潜力。未来需要进一步研究以验证这些结果并探索其临床意义。
Variances in the Expression Profile of Circadian Clock-Related Genes in Astrocytic Brain Tumors
肿瘤(癌症)患者之家