Department of Lung Cancer, Lung Cancer Center, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China.
Anat Rec (Hoboken). 2013 Jun;296(6):907-13. doi: 10.1002/ar.22700. Epub 2013 Apr 12.
Ikaros, encoded by the IKZF1 gene, is a pivotal transcription factor whose expression and utilization is dynamically altered during hematopoietic development. However, the molecular mechanisms controlling the transcription of the IKZF1 gene are unclear in lung cancer cell lines. Here we show the role of Ikaros in a cohort of grade IIIA lung cancer patients, with particular emphasis on its relationship with clinical outcomes and expression levels. The expression levels of Ikaros were positively correlated with the prognosis in the lung cancer patients. We also demonstrated that Ikaros expression is ectopically activated in a panel of lung cancer cell lines primarily through demethylation of its promoter. Moreover, gain-of-function experiments revealed that Ikaros inhibits migration and invasion of lung cancer cells in vitro. Our results thus shed light on how Ikaros can act as a lineage competency factor to facilitate lung cancer progression.
Ikaros 由 IKZF1 基因编码,是一种关键的转录因子,其表达和利用在造血发育过程中动态改变。然而,在肺癌细胞系中,控制 IKZF1 基因转录的分子机制尚不清楚。在这里,我们展示了 Ikaros 在一组 IIIA 期肺癌患者中的作用,特别强调了它与临床结果和表达水平的关系。Ikaros 的表达水平与肺癌患者的预后呈正相关。我们还证明,Ikaros 表达在外显子组的一组肺癌细胞系中通过其启动子的去甲基化而被异位激活。此外,功能获得实验表明,Ikaros 抑制肺癌细胞的迁移和侵袭。因此,我们的结果阐明了 Ikaros 如何作为谱系能力因子促进肺癌的进展。