School of Biological and Medical Physics, Moscow Institute of Physics and Technology, 141700 Dolgoprudny, Russia.
World-Class Research Center "Digital Biodesign and Personalized Healthcare", Sechenov First Moscow State Medical University, 119435 Moscow, Russia.
Int J Mol Sci. 2023 Feb 3;24(3):3042. doi: 10.3390/ijms24033042.
Radioresistance is a major obstacle for the successful therapy of many cancers, including non-small cell lung cancer (NSCLC). To elucidate the mechanism of radioresistance of NSCLC cells and to identify key molecules conferring radioresistance, the radioresistant subclones of p53 wild-type A549 and p53-deficient H1299 cell cultures were established. The transcriptional changes between parental and radioresistant NSCLC cells were investigated by RNA-seq. In total, expression levels of 36,596 genes were measured. Changes in the activation of intracellular molecular pathways of cells surviving irradiation relative to parental cells were quantified using the Oncobox bioinformatics platform. Following 30 rounds of 2 Gy irradiation, a total of 322 genes were differentially expressed between p53 wild-type radioresistant A549IR and parental A549 cells. For the p53-deficient (H1299) NSCLC cells, the parental and irradiated populations differed in the expression of 1628 genes and 1616 pathways. The expression of genes associated with radioresistance reflects the complex biological processes involved in clinical cancer cell eradication and might serve as a potential biomarker and therapeutic target for NSCLC treatment.
放射抵抗是许多癌症（包括非小细胞肺癌）成功治疗的主要障碍。为了阐明非小细胞肺癌细胞放射抵抗的机制并确定赋予放射抵抗的关键分子，建立了 p53 野生型 A549 和 p53 缺陷型 H1299 细胞培养物的放射抵抗亚克隆。通过 RNA-seq 研究了亲本和放射抵抗性 NSCLC 细胞之间的转录变化。总共测量了 36,596 个基因的表达水平。使用 Oncobox 生物信息学平台定量分析了细胞在照射后存活的细胞内分子途径的激活变化。经过 30 轮 2 Gy 照射后，p53 野生型放射抵抗 A549IR 与亲本 A549 细胞之间共有 322 个基因表达差异。对于 p53 缺陷型（H1299）非小细胞肺癌细胞，亲本和照射群体在 1628 个基因和 1616 个途径的表达上存在差异。与放射抵抗相关的基因表达反映了临床癌症细胞清除所涉及的复杂生物学过程，可能成为非小细胞肺癌治疗的潜在生物标志物和治疗靶标。
