Myocyte enhancer factor 2D provides a cross-talk between chronic inflammation and lung cancer.
Myocyte enhancer factor 2D provides a cross-talk between chronic inflammation and lung cancer.
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肌细胞增强因子 2D 提供了慢性炎症和肺癌之间的交互作用
DOI：
10.1186/s12967-017-1168-x
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发表时间：
2017-03-24
影响因子：
7.4
通讯作者：
Zhou JB
中科院分区：
文献类型：
--
作者：
Zhu HX;Shi L;Zhang Y;Zhu YC;Bai CX;Wang XD;Zhou JB
背景肺癌是世界范围内癌症相关发病率和死亡率的主要原因。患有慢性呼吸系统疾病，如慢性阻塞性肺病（COPD）的患者患肺癌的风险较高。慢性炎症可能在这些患者的肺癌发生中起重要作用。本研究旨在寻找预测慢性呼吸系统疾病患者肺癌风险的候选生物标志物。方法应用临床生物信息学工具对不同基因谱数据集进行分析，重点筛选慢性炎症-肺癌转化过程中潜在的生物标志物。然后，我们采用基于lps挑战的A549细胞的体外模型，通过rna测序、定量实时聚合酶链反应和western blot分析验证生物标志物。结果对基因表达Omnibus在线数据库中16个纳入的GSE数据集进行生物信息学分析显示，慢性阻塞性肺病合并非小细胞肺癌（NSCLC）患者的肌细胞增强因子2D （MEF2D）水平显著升高。炎症刺激增加了非小细胞肺癌A549细胞系中MEF2D的表达，且与炎症的严重程度相关。细胞外信号调节的蛋白激酶抑制可以逆转炎症激活A549中MEF2D的上调。MEF2D在NSCLC细胞的增殖、分化和运动等生物行为中发挥关键作用。结论炎性条件导致MEF2D表达升高，并可能通过影响肿瘤微环境和细胞生物学行为进一步促进肺癌的发生发展。MEF2D可能是慢性炎症-肺癌转化过程中的潜在生物标志物，可预测慢性呼吸系统疾病患者发生肺癌的风险。
BackgroundLung cancer is the leading cause of cancer-related morbidity and mortality worldwide. Patients with chronic respiratory diseases, such as chronic obstructive pulmonary disease (COPD), are exposed to a higher risk of developing lung cancer. Chronic inflammation may play an important role in the lung carcinogenesis among those patients. The present study aimed at identifying candidate biomarker predicting lung cancer risk among patients with chronic respiratory diseases.MethodsWe applied clinical bioinformatics tools to analyze different gene profile datasets with a special focus on screening the potential biomarker during chronic inflammation-lung cancer transition. Then we adopted an in vitro model based on LPS-challenged A549 cells to validate the biomarker through RNA-sequencing, quantitative real time polymerase chain reaction, and western blot analysis.ResultsBioinformatics analyses of the 16 enrolled GSE datasets from Gene Expression Omnibus online database showed myocyte enhancer factor 2D (MEF2D) level significantly increased in COPD patients coexisting non-small-cell lung carcinoma (NSCLC). Inflammation challenge increased MEF2D expression in NSCLC cell line A549, associated with the severity of inflammation. Extracellular signal-regulated protein kinase inhibition could reverse the up-regulation of MEF2D in inflammation-activated A549. MEF2D played a critical role in NSCLC cell bio-behaviors, including proliferation, differentiation, and movement.ConclusionsInflammatory conditions led to increased MEF2D expression, which might further contribute to the development of lung cancer through influencing cancer microenvironment and cell bio-behaviors. MEF2D might be a potential biomarker during chronic inflammation-lung cancer transition, predicting the risk of lung cancer among patients with chronic respiratory diseases.