In this paper, we have studied the role of chromosomal abnormalities in the expression of small nucleolar RNAs (snoRNAs) of radioresistant (K562) and radiosensitive (HL-60) leukemia cell line. Cells were exposed to an X-ray dose of 4 Gy. SnoRNA expression was investigated using NGS sequencing. The distribution of expressed snoRNAs on chromosomes has been found to be different for two cell lines. The most significant differences in the expression of snoRNAs were found in the K562 cell line based on the analysis of the dynamics of log2fc values. The type of clustering, the number and type of snoRNAs slightly differed in the chromosomes with trisomy and monosomy and had a pronounced difference in pairs with marker chromosomes in both cell lines. In this study, we have demonstrated that chromosomal abnormalities alter the expression of snoRNA after irradiation. Trisomies and monosomies do not have such a noticeable effect on the expression of snoRNAs as the presence of marker chromosomes.

The H/ACA snoRNA family is involved in pseudouridine biogenesis. It prevents genetic changes in cells and makes them more stable due to ribosomal RNA characteristics. Therefore, the study of H/ACA snoRNA expression in cell lines with chromosomal disorders after irradiation is of particular interest. The purpose of the study is to analyze the effect of chromosomal disorders on H/ACA snoRNA expression in radioresistant K562 and radiosensitive HL-60 cell lines after radiation exposure. Materials and Methods. K562 and HL-60 cell lines were exposed to radiation (4 Gy). H/ACA snoRNA expression was analyzed by NGS sequencing (1, 4, and 24 hours after irradiation). Results. The authors revealed differences in H/ACA snoRNA expression by chromosomes in the studied cell lines, as well as the impact of chromosomal abnormalities on H/ACA snoRNA expression after radiation exposure. Changes in the copy number of normal chromosomes lead to minor changes in H/ACA snoRNA expression. Marker chromosomes disrupt H/ACA snoRNA expression. Thus, is becomes impossible to use H/ACA snoRNAs located in abnormal chromosomes as radioresistance markers. Moreover, marker chromosomes decrease the number of H/ACA snoRNAs expressed in K562, despite the greater amount of genetic material.

The aim of the investigation was to study microRNA expression and its influence on signaling pathways activity in radioresistant and radiosensitive cell lines exposed to radiation.Materials and Methods. Radioresistant K562 cell line and radiosensitive HL-60 and Raji cell lines were used in the study. Cell survival was estimated after exposure to 4 Gy gamma radiation. MicroRNA composition was studied 1, 4 and 24 h after radiation exposure using massively parallel sequencing method. Bioinformatics analysis was performed using GenXpro and PANTHER database.Results. After single 4 Gy radiation exposure, the number of cells with the signs of necrosis increased several times in radiosensitive cell lines as compared to control samples. MicroRNA hsa-miR-590-3p was found in each studied cell line at every stage of the experiment. The most significant differences between radioresistant and radiosensitive cell lines were observed in dynamics of microRNA influence on Integrin signaling pathway and General transcription by RNA polymerase I pathway.Conclusion. MicroRNA hsa-miR-590-3p dynamics and expression level were found to correlate with cancer cell radiosensitivity. Its influence on radioresistant and radiosensitive cell lines was different: in radioresistant K562 cell line, the inhibitory effect of microRNA on Integrin signaling pathway was reduced and this effect on General transcription by RNA polymerase I pathway was increased.

Ischemic and reperfusion injury is a critical condition, as it is necessary to control cell death and maintain tissue function. Restoration of nutrient and oxygen flow causes secondary damage to ischemic cells and is called reperfusion injury. Reperfusion injury causes, on the one hand, fluctuations in ion concentration inside cells, in particular sodium ions, due to changes in the conductivity of voltage-dependent ion channels, and, on the other hand, activation of the antioxidant system as a response to oxidative stress, in which the key role is given to reactive oxygen species and nitric oxide. Thus, the effect of ion channel inhibitors on the progression of oxidative stress, apoptosis and necrosis during reperfusion is of particular interest. The aim of the study is to examine the impact of sodium channels on oxidative stress under ischemic and reperfusion injury and sodium channel blockers action. Materials and Methods. The authors studied the influence of the synthesized peptide toxin, an inhibitor of voltage-gated sodium channels, under modelled ischemia/reperfusion in CHO-K1 culture on the level of apoptosis, necrosis, and oxidative stress (concentration of reactive oxygen species, nitric oxide, and glutathione) using fluorescent dyes and fluorescence microplate reader. Results. Data obtained indicate a decreased level of apoptosis and necrosis, and a control level of nitric oxide under toxin at a nanomolar concentration. At the same time, the concentrations of reactive oxygen species and glutathione did not change. Thus, the inhibitor toxin acted as a protective agent by preventing a decrease in the nitric oxide concentration, which favorably affected the survival of the cell culture during reperfusion after ischemia.

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.