Abstract：
Lung cancer is one of the most prevalent human cancers with a high lethality rate worldwide. In this study, we demonstrated that GSE1 (genetic suppressor element 1) expression is aberrantly upregulated in lung adenocarcinoma and that GSE1 depletion inhibits the proliferation and migration of both A549 and H1299 cells. Immunoprecipitation assays demonstrated that GSE1 interacts with histone deacetylase 1 (HDAC1) and other BRAF-HDAC complex (BHC) components in cells. The transcriptome of GSE1-knockdown A549 cells indicated that 207 genes were upregulated and 159 were downregulated based on a p-value < .05 and fold change ≥ 1.5. Bioinformatics analysis suggested that 140 differentially expressed genes harbor binding sites for HDAC1, including the tumor suppressor gene KLF6 (Kruppel-like factor 6). Indeed, quantitative reverse-transcription polymerase chain reaction and western blot analysis revealed that GSE1 could inhibit the transcription of KLF6 in lung cancer cells. In conclusion, GSE1 cooperates with HDAC1 to promote the proliferation and metastasis of non-small cell lung cancer cells through the downregulation of KLF6 expression.
摘要：
肺癌是世界范围内最普遍的人类癌症之一，具有很高的致死率。在这项研究中,我们证明GSE1(遗传抑制因子1)表达在肺腺癌中异常上调,GSE1耗竭抑制A549和H1299细胞的增殖和迁移.免疫沉淀实验表明，GSE1与细胞中的组蛋白脱乙酰酶1（HDAC1）和其他BRAF-HDAC复合物（BHC）成分相互作用。GSE1敲低A549细胞的转录组表明，基于p值<.05和倍数变化≥1.5，207个基因上调，159个基因下调。生物信息学分析表明，140个差异表达基因含有HDAC1的结合位点，包括抑癌基因KLF6（Kruppel样因子6）。的确,定量逆转录聚合酶链反应和蛋白质印迹分析显示GSE1可抑制肺癌细胞中KLF6的转录。总之,GSE1与HDAC1协同作用，通过下调KLF6的表达促进非小细胞肺癌细胞的增殖和转移。
