Effects of EVI1 and EVI1Δ324 mild expression in HeLa cells. Homo sapiens

We studied the variations of mRNA amounts after Flag-EVI1, Flag-EVI1Δ324, or Flag expression in HeLa cells. Despites EVI1 discovery in 1988, its recognized role as a dominant oncogene in myeloid leukemia and more recently in epithelial cancers, only a few target genes were known and it was not clear why EVI1 was involved in cancer progression. Here we obtained the genomic binding occupancy and expression data for EVI1 in human cells. We identified numerous EVI1 target cancer genes and genes controlling cell migration and adhesion. Moreover, we characterized a transcriptional cooperation between AP1 and EVI1 that regulated proliferation and adhesion through a feed-forward loop. This study provides human genome-wide mapping and expression analyses for EVI1 that will be useful for the research community. Overall design: 12 samples were collected. Each condition was done in 4 replicates, collected 24 hours after transfection (for mild expression of EVI1 or EVI1Δ324). Transfections with Flag-expressing vector were used as controls.

本研究探究了海拉细胞（HeLa）中分别过表达Flag-EVI1、Flag-EVI1Δ324及空Flag表达载体后，细胞内信使RNA（mRNA）水平的变化情况。尽管EVI1早在1988年即被发现，且已被证实为髓系白血病的显性致癌基因，近年研究还揭示其在上皮源性癌症中的致癌作用，但目前已知的EVI1靶基因数量极少，且其参与癌症进展的具体机制仍不明确。本研究获取了人类细胞中EVI1的全基因组结合占据谱与基因表达谱数据，鉴定出大量EVI1的癌症相关靶基因以及调控细胞迁移与黏附的功能基因。此外，本研究还阐明了转录因子AP1与EVI1之间的转录协同作用——二者通过前馈环路调控细胞增殖与黏附过程。本研究完成了人类全基因组范围内的EVI1结合位点定位与表达分析，相关数据可为相关科研领域提供重要参考。实验整体设计：共收集12份样本。所有实验组均设置4次生物学重复，于转染后24小时（此时EVI1或EVI1Δ324呈轻度表达）收集样本；以转染空Flag表达载体的样本作为对照组。