Genome-wide binding signature of Signal transducer and activator of transcription (STAT) family in colorectal cancer HCT 116 cell

The excessive and continuous activated Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway leads to the proliferation and migration of malignant cells resulting in the occurrence and development of almost all of cancers. The defined gene sets specifically activated by different STAT proteins are relied on their genomic accessibility by the interplay of certain STAT proteins with other potential cofactors. However, we have no clue about the status of human activated STAT dimers in the nucleus, as well as the intercrossing modules of synergic, supplementary or competitive relationship among each other in colorectal cancer. In current study, chromatin immunoprecipitation sequencing (ChIP-seq) was conducted to explore the genome-scale binding signatures of STAT1, STAT2, STAT3, STAT5A/B and STAT6 in human HCT-116 CRC cells. Moreover, STAT3 binding on genomic DNA was also investigated in HCT116 cells with NR5A2 knockdown.

过度且持续激活的贾纳斯激酶/信号转导与转录激活因子（Janus kinase/signal transducer and activator of transcription, JAK/STAT）通路可促使恶性细胞增殖与迁移，进而导致几乎所有癌症的发生与发展。由不同STAT蛋白特异性激活的特定基因集，其基因组可及性依赖于特定STAT蛋白与其他潜在辅因子之间的相互作用。然而，目前我们对结直肠癌中处于激活状态的人类STAT二聚体在细胞核内的分布情况，以及各STAT蛋白间协同、补充或竞争性关系的互作模块仍不甚明晰。本研究采用染色质免疫沉淀测序（chromatin immunoprecipitation sequencing, ChIP-seq）技术，对人类HCT-116结直肠癌细胞（colorectal cancer, CRC）中STAT1、STAT2、STAT3、STAT5A/B及STAT6的全基因组结合特征进行了探究。此外，本研究还对NR5A2基因敲低的HCT-116细胞中STAT3与基因组DNA的结合情况进行了分析。