In our study, we estimate an effect from chromosome aberrations and genome mutations on changes in microRNA expression profiles in cancer cell lines demonstrating different radiosensitivity. Here, cell viability and microRNA spectrum have been estimated 1, 4, and 24 h after irradiation. MiSeq high-throughput sequencing system (Illumina, San Diego, CA, USA) is employed to perform microRNA spectrum estimation. In the K562 cell line, the number of expressed microRNAs in chromosomes demonstrates a more pronounced variation. An analysis of microRNA effects on signaling pathway activity demonstrates differences in post-transcriptional regulation of the expression of genes included into 40 signaling pathways. In the K562 cell line, microRNA dynamics analyzed for their dependence on chromosome localization show a wider scattering of microRNA expression values for a pair of chromosomes compared to the HL-60 cell line. An analysis of microRNAs expression in the K562 and HL-60 cell lines after irradiation has shown that chromosome abnormalities can affect microRNA expression changes. A study of radiation-induced changes of microRNA expression profiles in the K562 and HL-60 cell lines has revealed a dependence of microRNA expression changes on the number of chromosome aberrations and genome mutations.

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Ischemia-reperfusion injury (IRI) is an irreversible functional and structural injury. Restoration of normal oxygen concentration exacerbates the emergence and development of deadly cells. One of the possible moments of reperfusion damage to cells is an increase in the intracellular concentration of sodium ions. In this article, we study the mu-agatoxin-Aa1a, a modulator of sodium channels, on the processes of IRI cells damage. The toxin was synthesized using an automatic peptide synthesizer. Hypoxia was induced by reducing the content of serum and oxygen in the CHO-K1 culture. The influence of the toxin on the level of apoptosis; intracellular concentration of sodium, calcium, and potassium ions; intracellular pH; totality of reactive oxygen species (ROS), nitric oxide (NO), and ATP; and changes in the mitochondrial potential were studied. The experiments performed show that mu-agatoxin-Aa1a effectively prevents IRI of cells. Toxin reduces the level of apoptosis and prevents a decrease in the intracellular concentration of sodium and calcium ions during IRI. Mu-agatoxin-Aa1a contributes to the maintenance of elevated intracellular pH, reduces the intracellular concentration of ROS, and prevents the decrease in intracellular NO concentration and mitochondrial potential under conditions of reoxygenation/reperfusion. An analysis of experimental data shows that the mu-agatoxin-Aa1a peptide has adaptogenic properties. In the future, this peptide can be used to prevent ischemia/reperfusion tissue damage different genesis.

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.

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.