期刊
LUNG CANCER
卷 72, 期 1, 页码 92-99出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.lungcan.2010.07.014
关键词
miRNA; Radiotherapy sensitivity; Apoptosis; NSCLC
资金
- National Natural Science Foundation of China [30901723]
- Research Fund for the Doctoral Program of Higher Education of China [200800231052]
- Natural Science Foundation of Tianjin [08JCYBJC07300]
- CMB [A2009002]
- Institute fund of Radiation Medicine [SR0815]
Purpose: To investigate the different miRNA expression profiles of postoperative radiotherapy sensitive and resistant patients of non-small cell lung cancer, explore their potential role and find some radiosensitivity markers. Materials and methods: Thirty non-small cell lung cancer patients who have been treated by postoperative radiotherapy were selected and were divided into radiotherapy sensitive group and resistant group according to overall survival and local or distant recurrence rate. Expression profile of miRNA in these two groups was detected by a microarray assay and the results were validated by quantitative RT-PCR and Northern blot. At the molecular level, the effect of one differently expressed miRNA (miR-126) on the growth and apoptosis of SK-MES-1 cells induced by irradiation was examined. Results: Comparing with resistant patients, five miRNAs (miRNA-126, miRNA-let-7a, miRNA-495, miRNA-451 and miRNA-128b) were significantly upregulated and seven miRNAs (miRNA-130a, miRNA-106b, miRNA-19b, miRNA-22, miRNA-15b, miRNA-17-5p and miRNA-21) were greatly downregulated in radiotherapy sensitive group. Overexpression of miRNA-126 inhibited the growth of SK-MES-1 cells and promoted its apoptosis induced by irradiation. The expression level of p-Akt decreased in miRNA-126 overexpression group. After treating with phosphoinositidy1-3 kinase (PI3K) constitutively activator (IGF-1) and inhibitor (LY294002), miRNA-126 overexpression had no significant effects on the apoptosis of SK-MES-1 cells. Conclusion: We found 12 differently expressed miRNAs in the radiotherapy sensitive and resistant non-small cell lung cancer samples. Moreover, our results showed miRNA-126 promoted non-small cell lung cancer cells apoptosis induced by irradiation through the PI3K-Akt pathway. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
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