Bone morphogenetic protein-focused strategies to induce cytotoxicity in lung cancer cells.
Bone morphogenetic protein-focused strategies to induce cytotoxicity in lung cancer cells.
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发表时间：
2014-05
影响因子：
2
通讯作者：
A. Fotinos;Narayani Nagarajan;Adriano S. Martins;D. Fritz;D. Garsetti;Annette Lee;C. Hong;M. Rogers
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文献类型：
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作者：
A. Fotinos;Narayani Nagarajan;Adriano S. Martins;D. Fritz;D. Garsetti;Annette Lee;C. Hong;M. Rogers
背景：骨形态发生蛋白-2在肺癌中的高表达与患者预后不良有关。本研究探索了抑制BMP信号转导的策略。材料与方法在转化和未转化的肺细胞中检测BMP2基因敲除、多索吗啡衍生物和microRNAs的细胞毒性。对A549肺腺癌细胞和与BEAS-2B支气管上皮细胞相关的另外两种转化的肺细胞中的1,145个microRNA进行了微阵列分析。结果BMP2合成减少抑制了A549细胞的生长。吗啡衍生物LDN-193189对A549细胞有较强的细胞毒作用，但对BEAS-2B细胞无明显杀伤作用。基因芯片分析显示，在3个转化系中，有106个miRNAs表达下调，69个miRNAs表达上调。3个下调的miRNAs，hsa-mir-34b，hsa-mir-34c-3p和hsa-miR-486-3p抑制了BMP2报告基因，对A549细胞有细胞毒作用，但对BEAS-2B细胞没有影响。结论观察到的细胞毒作用表明，减少BMP信号转导是肺癌治疗的一条有效途径。
BACKGROUND High bone morphogenetic protein (BMP)-2 expression in lung carcinoma correlates with poor patient prognosis. The present study explored strategies to repress BMP signaling. MATERIALS AND METHODS The cytotoxicity of BMP2-knockdown, dorsomorphin derivatives, and microRNAs was tested in transformed and non-transformed lung cells. Microarray analyses of 1,145 microRNAs in A549 lung adenocarcinoma cells and two other transformed lung cell types relative to BEAS-2B bronchial epithelial cells were performed. RESULTS Reduced BMP2 synthesis inhibited A549 cell growth. The dorsomorphin derivative LDN-193189, but not DMH1 or DMH4, was strongly cytotoxic towards A549 cells, but not towards BEAS-2B cells. Microarray analysis revealed that 106 miRNAs were down-regulated and 69 miRNAs were up-regulated in the three transformed lines. Three down-regulated miRNAs, hsa-mir-34b, hsa-mir-34c-3p, and hsa-miR-486-3p, repressed a BMP2 reporter gene and were cytotoxic in A549 cells, but not towards BEAS-2B cells. CONCLUSION The observed cytotoxicity suggests that reducing BMP signaling is a useful line of attack for therapy of lung cancer.