Staszkiewicz Rafał, Sobański Dawid, Pulka Wojciech, Gładysz Dorian, Gadzieliński Marcin, Strojny Damian, Grabarek Beniamin Oskar
Collegium Medicum, WSB University, 41-300 Dabrowa Gornicza, Poland.
Department of Neurosurgery, 5th Military Clinical Hospital with the SP ZOZ Polyclinic in Krakow, 30-901 Cracow, Poland.
Cancers (Basel). 2024 Jun 26;16(13):2335. doi: 10.3390/cancers16132335.
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 , protein kinase AMP-activated catalytic subunit alpha 1 , protein kinase AMP-activated catalytic subunit alpha 2 , protein kinase AMP-activated non-catalytic subunit beta 1 , protein kinase AMP-activated non-catalytic subunit beta 2 , period circadian regulator 1 , period circadian regulator 2 () and period circadian regulator 3 , 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时钟基因在星形细胞瘤（一种常见的脑肿瘤类型）进展中的作用。目的是评估这些基因与肿瘤分级相关的表达模式。我们使用微阵列分析、定量逆转录聚合酶链反应（qRT-PCR）和甲基化特异性PCR，检测了60例患者肿瘤样本中的基因表达、DNA甲基化模式和微小RNA相互作用。我们的结果表明，关键的昼夜节律时钟基因，如昼夜节律调节因子、蛋白激酶AMP激活的催化亚基α1、蛋白激酶AMP激活的催化亚基α2、蛋白激酶AMP激活的非催化亚基β1、蛋白激酶AMP激活的非催化亚基β2、昼夜节律调节因子1、昼夜节律调节因子2（）和昼夜节律调节因子3的表达，随肿瘤分级而有显著差异。值得注意的是，在高级别肿瘤中观察到CLOCK基因表达和蛋白水平增加。DNA甲基化分析显示，PER1 - 3基因的启动子区域持续甲基化，提示了其表达降低的一种机制。我们的研究结果还强调了涉及微小RNA（如hsa-miR-106-5p、hsa-miR-20b-5p和hsa-miR-30d-3p）的复杂调控机制，这些微小RNA会影响昼夜节律时钟相关基因的表达。这突出了昼夜节律时钟基因在星形细胞瘤进展中的重要性，并强调了它们作为生物标志物和治疗靶点的潜力。需要进一步的研究来验证这些结果并探索其临床意义。
