Genetic and expression variations of cell cycle pathway genes in brain tumor patients

Abstract

The present study was designed to determine the association between the genetic polymorphisms/expression variations of RB1 and CCND1 genes and brain tumor risk. For this purpose, 250 blood samples of brain tumor patients along with 250 controls (cohort I) and 96 brain tumor tissues (cohort II) with adjacent control section were collected. Mutation analysis of RB1 (rs137853294, rs121913300) and CCND1 (rs614367, rs498136) genes was performed using ARMS-PCR followed by sequencing, and expression analysis was performed using real-time PCR and immunohistochemistry. The results showed homozygous mutant genotype of RB1 gene polymorphism, rs121913300 (P=0.003) and CCND1 gene polymorphism rs614367 (P=0.01) were associated significantly with brain tumor risk. Moreover, significant down-regulation of RB1 (P=0.005) and up-regulation of CCND1 (P=0.0001) gene was observed in brain tumor sections vs controls. Spearman correlation showed significant negative correlation between RB1 vs proliferation marker, Ki-67 (r = −0.291*, P<0.05) in brain tumors. Expression levels of selected genes were also assessed at protein level using immunohistochemical analysis (IHC) and signification down-regulation of RB1 (P=0.0001) and up-regulation of CCND1 (P=0.0001) was observed in brain tumor compared with control sections. In conclusion, it is suggested that polymorphisms/expression variations of RB1 and CCND1 genes may be associated with increased risk of brain tumor.

Inhibitory effect of Fingolimod on head and neck squamous cell carcinoma and its mechanism: Gene set enrichment analysis

“…However, the application of CDK4/6 inhibitor to tumor tissues showed a significantly decreased proliferative activity in breast cancer and a significantly increased cellular senescence and apoptosis. Meanwhile, CDK4/6 inhibitor has a good application effect in acute T lymphocytic leukemia, melanoma and non-small-cell lung cancer (22)(23)(24). On this basis, Western blot assay verified the significantly inhibited expression of CyclinD1, CDK4 and CDK6 and the increased expression of p-CDK4 and p-CDK6 after adding Fingolimod in this study.…”

M2 Muscarinic Receptor Activation Impairs Mitotic Progression and Bipolar Mitotic Spindle Formation in Human Glioblastoma Cell Lines

“…Glioblastoma cells are characterized by an aberrant cell cycle [ 20 ] and marked aneuploidy [ 21 ]. Therefore, mitotic catastrophe induction may be an interesting oncosuppressive mechanism with the aim of inducing mitosis-related cell death or permanent cell cycle arrest [ 23 ].…”

“…In recent years, a wide range of clinically employed and experimental anticancer agents arresting the cell cycle and triggering apoptosis have started emerging [ 19 ]. Like other solid tumors, GB cells show an aberrant cell cycle and an increased rate of proliferation [ 20 ], as well as marked aneuploidy [ 21 ], suggesting that one of the causes of chromosomal instability could be determined by deregulated checkpoints.…”

Aberrant Cyclin D1 splicing in cancer: from molecular mechanism to therapeutic modulation

“…Therefore, the G870A mutation of CCND1 may be a key risk factor for cancers. In addition, other mutations of CCND1 have been studied, such as rs614367, rs498136, and rs7177 [92,93]. In the future, we need to further study the role of these mutations in cancers.…”