Tianjin Key Laboratory of Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Science, Tianjin 300192, China.
Lung Cancer. 2011 Apr;72(1):92-9. doi: 10.1016/j.lungcan.2010.07.014. Epub 2010 Aug 21.
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 radio-sensitivity markers.
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.
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 phosphoinositidyl-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.
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.
研究非小细胞肺癌术后放疗敏感和抵抗患者的不同 miRNA 表达谱，探讨其潜在作用，并寻找一些放射敏感性标志物。
选择 30 例接受术后放疗的非小细胞肺癌患者，根据总生存率和局部或远处复发率将其分为放疗敏感组和抵抗组。通过微阵列分析检测两组患者的 miRNA 表达谱，并用定量 RT-PCR 和 Northern blot 进行验证。在分子水平上，检测一个差异表达的 miRNA（miR-126）对 SK-MES-1 细胞照射诱导的生长和凋亡的影响。
与抵抗组患者相比，放疗敏感组中有 5 个 miRNA（miR-126、miR-let-7a、miR-495、miR-451 和 miR-128b）显著上调，7 个 miRNA（miR-130a、miR-106b、miR-19b、miR-22、miR-15b、miR-17-5p 和 miR-21）显著下调。miR-126 的过表达抑制 SK-MES-1 细胞的生长，并促进其照射诱导的凋亡。过表达 miR-126 组中 p-Akt 的表达水平降低。用磷脂酰肌醇-3 激酶（PI3K）组成型激活剂（IGF-1）和抑制剂（LY294002）处理后，miR-126 的过表达对 SK-MES-1 细胞的凋亡没有显著影响。
我们在放疗敏感和抵抗的非小细胞肺癌样本中发现了 12 个差异表达的 miRNA。此外，我们的结果表明，miR-126 通过 PI3K-Akt 通路促进非小细胞肺癌细胞照射诱导的凋亡。
