Objectives: Radiotherapy has played a limited role in the treatment of non-small cell lung cancer (NSCLC) due to the risk of tumour radioresistance. We previously established the radioresistant non-small cell lung cancer (NSCLC) cell line H460R. In this study, we identified differentially expressed genes between these radioresistant H460R cells and their radiosensitive parent line. We further evaluated the role of a differentially expressed gene, ITGB1, in NSCLC cell radioresistance and as a potential target for improving radiosensitivity./nMaterials and Methods: The radiosensitivity of NSCLC cells was evaluated by flow cytometry, colony formation assays, immunofluorescence, and Western blotting. Bioinformatics assay was used to identify the effect of ITGB1 and YAP1 expression in NSCLC tissues./nResults: ITGB1 mRNA and protein expression levels were higher in H460R than in the parental H460 cells. We observed lower clonogenic survival and cell viability and a higher rate of apoptosis of ITGB1-knockdown A549 and H460R cells than of wild type cells post-irradiation. Transfection with an ITGB1 short hairpin (sh) RNA enhanced radiation-induced DNA damage and G2/M phase arrest. Moreover, ITGB1 induced epithelial-mesenchymal transition (EMT) of NSCLC cells. Silencing ITGB1 suppressed the expression and intracellular translocation of Yes-associated protein 1 (YAP1), a downstream effector of ITGB1./nConclusions: ITGB1 may induce radioresistance via affecting DNA repair and YAP1-induced EMT. Taken together, our data suggest that ITGB1 is an attractive therapeutic target to overcome NSCLC cell radioresistance.

中文翻译：

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ITGB1 通过调节 DNA 损伤反应和 YAP1 诱导的上皮间充质转化来增强人类非小细胞肺癌细胞的放射抗性

目的：由于存在肿瘤放射抗性的风险，放射治疗在非小细胞肺癌 (NSCLC) 的治疗中发挥的作用有限。我们之前建立了抗辐射非小细胞肺癌 (NSCLC) 细胞系 H460R。在这项研究中，我们确定了这些抗辐射 H460R 细胞与其对辐射敏感的亲代细胞之间差异表达的基因。我们进一步评估了差异表达基因 ITGB1 在 NSCLC 细胞放射抗性中的作用以及作为提高放射敏感性的潜在靶标。/n材料和方法：通过流式细胞术、集落形成测定、免疫荧光和蛋白质印迹。生物信息学检测用于鉴定ITGB1和YAP1在NSCLC组织中表达的影响。/n结果： H460R 细胞中 ITGB1 mRNA 和蛋白表达水平高于亲本 H460 细胞。我们观察到 ITGB1 敲低的 A549 和 H460R 细胞在辐照后的克隆存活率和细胞活力较低，凋亡率高于野生型细胞。用 ITGB1 短发夹 (sh) RNA 转染增强了辐射诱导的 DNA 损伤和 G2/M 期停滞。此外，ITGB1 诱导 NSCLC 细胞的上皮间质转化 (EMT)。沉默 ITGB1 抑制了 Yes 相关蛋白 1 (YAP1) 的表达和细胞内易位，它是 ITGB1 的下游效应物。/n结论：ITGB1 可能通过影响 DNA 修复和 YAP1 诱导的 EMT 来诱导放射抗性。总之，我们的数据表明 ITGB1 是克服 NSCLC 细胞放射抗性的有吸引力的治疗靶点。