系统生物学方法筛选人肺巨细胞癌细胞株转移相关miRNA的研究

Detection of metastasis-related miRNA in human lung giant cell carcinoma cell strains via systems biology

目的:探讨人低转移肺巨细胞癌细胞株95C和人高转移肺巨细胞癌细胞株95D中微小RNA(microRNA,miR-NA)的差异性表达,分析差异表达miRNA在肺癌细胞转移调控网络中的作用。方法:常规培养95C和95D,分别提取总RNA并进行质检;应用微阵列芯片检测miRNAs的表达,并对其表达谱进行差异性分析;从系统生物学角度,应用生物信息学的研究方法,分析肺癌转移可能相关的异常表达miRNA与相应靶基因。结果:两者miRNA表达存在显著差异,与95C细胞相比,在95D中上调>1.5倍的miRNA有36条,下调>1.5倍的miRNA有19条;12条差异表达miR-NA及1 046个预测靶基因构成了肺癌转移相关调控网络。结论:获得了人低转移肺巨细胞癌细胞株95C和人高转移肺巨细胞癌细胞株95D的差异miRNA表达谱,初步构建了一个由差异miRNA及其靶基因组成的复杂肺癌转移相关调控网络,分析发现部分miRNA为调控网络的关键节点。

OBJECTIVE： To screen lung cancer metastasis-associated miRNA by analysis of differentially expressed genes between human lung giant cell carcinoma cell strains of low metastatic 95C and high metastatic 95D using micorna microarray. METHODS：95C and 95D cells were cultured, the total RNA was isolated and examined The expression profiles of miRNA were detected with miRNA microarray chip. Potential miRNA targets were analyzed by bioinformatics. RE- SULTS.. According to the microarray screening, 36 were up-regulated and 19 down-regulated. Twelve different-expressed miRNA and 1 046 candidate targeted genes were identified that formed a regulatory network. CONCLUSIONS.. The miR- NA expression profiles of low metastatic 95C and high metastatic 95D are obtained. We present a comprehensive overview of the molecular networks perturbed in the metastasis of lung cancer, discuss several potential key molecular regulatory circuits,and identify microRNA species that may play central roles in facilitating the metastasis of lung cancer.