IMPACT OF THE GENE EXPRESSION LEVEL AND INTERMOLECULAR INTERACTION NETWORKS ON RADIORESISTANCE OF TUMOR CELLS

E. Pogodina, E. Rastorgueva, E. Yurova, E. Beloborodov, D. Sugak, Y. Saenko, A. N. Fomin, Maksim Anatol'evich Volkov, B. M. Kostishko
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Abstract

Despite its efficacy, radiation therapy faces the challenges connected with accelerated reproduction of tumor cells and radioresistance of malignant neoplasms. The aim of the study was to analyze the impact of the gene expression level and intermolecular interaction networks on the development of tumor cell radioresistance. Materials and Methods. The authors used 4 tumor cell lines: (K562, HCT-116p53 (+/+), HCT-116p53 (–/–), and Me45. To study the cell line transcriptome. Affymetrix high-density hybridization DNA chips (HGU133A series) were used. Bioinformatic analysis of gene expression dynamics was performed using the original Gene Selector program. Intermolecular interaction networks were studied using the STRING online system. Results. After exposure to ionizing radiation at a dose of 4 Gy, the expression level of DAAM1, IFNAR2, PALLD, and STK17A genes increases in K562 cell line and decreases in HCT-116p53 (+/+), HCT-116p53 (–/–) and Me45. Numerous protein complexes of the studied genes were found with STRING online system. Thus, DAAM1, IFNAR2, PALLD, and STK17A genes influence the activity of some particles in the network of intermolecular interactions. Selected DAAM1, IFNAR2, PALLD and STK17A genes and protein-protein complexes encoded by DAAM1, TNK2, PTBP2 and DVL2; IFNAR2, STAT2, IRF9, JAK1, GNB2L1 and IFNAR1; PALLD, LPP and ACTN2 genes can be used as potential targets. Their modulation can increase the response of malignant neoplasm cells to ionizing radiation.
基因表达水平和分子间相互作用网络对肿瘤细胞放射耐药的影响
放射治疗虽有疗效,但也面临肿瘤细胞繁殖加速和恶性肿瘤放射耐药的挑战。本研究的目的是分析基因表达水平和分子间相互作用网络对肿瘤细胞放射耐药发展的影响。材料与方法。作者使用4种肿瘤细胞系:(K562)、HCT-116p53(+/+)、HCT-116p53(- / -)和Me45。研究细胞系转录组。采用Affymetrix高密度杂交DNA芯片(HGU133A系列)。基因表达动态的生物信息学分析使用原始的基因选择程序进行。利用STRING在线系统对分子间相互作用网络进行了研究。结果。4 Gy电离辐射照射后,K562细胞系DAAM1、IFNAR2、PALLD和STK17A基因表达水平升高,HCT-116p53(+/+)、HCT-116p53(- / -)和Me45表达水平降低。在STRING在线系统中发现了许多研究基因的蛋白质复合物。因此,DAAM1、IFNAR2、pald和STK17A基因影响分子间相互作用网络中某些颗粒的活性。选择DAAM1、IFNAR2、pald、STK17A基因及DAAM1、TNK2、PTBP2、DVL2编码的蛋白复合物;IFNAR2、STAT2、IRF9、JAK1、GNB2L1和IFNAR1;pald、LPP和ACTN2基因可作为潜在靶点。它们的调节可以增加恶性肿瘤细胞对电离辐射的反应。
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