BACKGROUND Non-small cell lung cancer (NSCLC) is one of the leading causes of death in the world. NSCLC diagnosed at an early stage can be highly curable with a positive prognosis, but biomarker limitations make it difficult to diagnose lung cancer at an early stage. To identify biomarkers for lung cancer development, we previously focused on the oncogenic roles of transcription factor TFAP2C in lung cancers and revealed the molecular mechanism of several oncogenes in lung tumorigenesis based on TFAP2C-related microarray analysis. RESULTS In this study, we analyzed microarray data to identify tumor suppressor genes and nine genes downregulated by TFAP2C were screened. Among the nine genes, we focused on growth arrest and DNA-damage-inducible beta (GADD45B) and phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1) as representative TFAP2C-regulated tumor suppressor genes. It was observed that overexpressed TFAP2C resulted in inhibition of GADD45B and PMAIP1 expressions at both the mRNA and protein levels in NSCLC cells. In addition, downregulation of GADD45B and PMAIP1 by TFAP2C promoted cell proliferation and cell motility, which are closely associated with NSCLC tumorigenesis. CONCLUSION This study indicates that GADD45B and PMAIP1 could be promising tumor suppressors for NSCLC and might be useful as prognostic markers for use in NSCLC therapy.

中文翻译：

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TFAP2C通过下调非小细胞肺癌细胞中的GADD45B和PMAIP1来增加细胞增殖。

背景技术非小细胞肺癌（NSCLC）是世界上主要的死亡原因之一。早期诊断为NSCLC可以高度治愈，且预后良好，但是生物标志物的局限性使得早期诊断肺癌非常困难。为了鉴定肺癌发展的生物标志物，我们先前集中于转录因子TFAP2C在肺癌中的致癌作用，并基于TFAP2C相关的微阵列分析揭示了几种致癌基因在肺癌发生中的分子机制。结果在这项研究中，我们分析了微阵列数据以鉴定肿瘤抑制基因，并筛选了由TFAP2C下调的9个基因。在这九个基因中 我们专注于作为典型的TFAP2C调控肿瘤抑制基因的生长停滞和DNA损伤诱导性beta（GADD45B）和phorbol-12-肉豆蔻酸13-乙酸酯诱导的蛋白1（PMAIP1）。观察到过表达的TFAP2C导致NSCLC细胞中mRNA和蛋白水平的GADD45B和PMAIP1表达受到抑制。此外，TFAP2C对GADD45B和PMAIP1的下调促进了细胞增殖和细胞运动，这与NSCLC的肿瘤发生密切相关。结论这项研究表明GADD45B和PMAIP1可能是NSCLC的有希望的肿瘤抑制因子，并可能用作NSCLC治疗的预后标志物。此外，TFAP2C对GADD45B和PMAIP1的下调促进了细胞增殖和细胞运动，这与NSCLC的肿瘤发生密切相关。结论这项研究表明GADD45B和PMAIP1可能是NSCLC的有希望的肿瘤抑制因子，并可能用作NSCLC治疗的预后标志物。此外，TFAP2C对GADD45B和PMAIP1的下调促进了细胞增殖和细胞运动，这与NSCLC的肿瘤发生密切相关。结论这项研究表明GADD45B和PMAIP1可能是NSCLC的有希望的肿瘤抑制因子，并可能用作NSCLC治疗的预后标志物。