ITGB1 enhances the Radioresistance of human Non-small Cell Lung Cancer Cells by modulating the DNA damage response and YAP1-induced Epithelial-mesenchymal Transition.
ITGB1 enhances the Radioresistance of human Non-small Cell Lung Cancer Cells by modulating the DNA damage response and YAP1-induced Epithelial-mesenchymal Transition.
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DOI：
10.7150/ijbs.52319
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发表时间：
2021
影响因子：
9.2
通讯作者：
Zou H
中科院分区：
文献类型：
--
作者：
Li Y;Sun C;Tan Y;Zhang H;Li Y;Zou H
目的：放射治疗在非小细胞肺癌（NSCLC）的治疗中发挥了有限的作用，由于肿瘤放射抵抗的风险。我们先前建立了放射抗性非小细胞肺癌（NSCLC）细胞系H460 R。在这项研究中，我们确定了差异表达的基因之间的这些辐射抗性H460 R细胞和它们的辐射敏感的亲本系。我们进一步评估了差异表达基因ITGB 1在NSCLC细胞放射抗性中的作用，并作为提高放射敏感性的潜在靶点。材料与方法：通过流式细胞术、集落形成试验、免疫荧光和Western印迹法评价NSCLC细胞的放射敏感性。采用生物信息学方法分析ITGB 1和YAP 1在NSCLC组织中表达的影响。结果：ITGB 1在H460 R细胞中的mRNA和蛋白表达水平均高于亲本细胞。我们观察到较低的克隆存活率和细胞活力和较高的凋亡率ITGB 1敲低A549和H460 R细胞比野生型细胞照射后。转染ITGB 1短发夹RNA可增强辐射诱导的DNA损伤和G2/M期阻滞。此外，ITGB 1诱导NSCLC细胞的上皮间质转化（EMT）。沉默ITGB 1抑制了Yes相关蛋白1（YAP 1）的表达和细胞内转运，YAP 1是ITGB 1的下游效应子。结论：ITGB 1可能通过影响DNA修复和YAP 1诱导的EMT而诱导辐射抗性。总之，我们的数据表明ITGB 1是克服NSCLC细胞放射抗性的有吸引力的治疗靶点。
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. Materials 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. Results: 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. Conclusions: 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.
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影响因子：
19
作者：
Ceccaldi R;Rondinelli B;D'Andrea AD
通讯作者：
D'Andrea AD
影响因子：
8
作者：
Ciamporcero E;Shen H;Ramakrishnan S;Yu Ku S;Chintala S;Shen L;Adelaiye R;Miles KM;Ullio C;Pizzimenti S;Daga M;Azabdaftari G;Attwood K;Johnson C;Zhang J;Barrera G;Pili R
通讯作者：
Pili R
影响因子：
11.2
作者：
Carbonell WS;DeLay M;Jahangiri A;Park CC;Aghi MK
通讯作者：
Aghi MK
影响因子：
5.7
作者：
Hehlgans, Stephanie;Eke, Iris;Cordes, Nils
通讯作者：
Cordes, Nils
影响因子：
5.8
作者：
Chen, Hsiu-Mei;Lin, Yi-Hsuan;Tsai, Shaw-Jenq
通讯作者：
Tsai, Shaw-Jenq