Center for Experimental Medicine, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China; Jiangxi Key Laboratory of Molecular Diagnostics and Precision Medicine, Nanchang, Jiangxi 330006, China.
Center for Experimental Medicine, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China; School of Pharmacy, Nanchang University, Nanchang, Jiangxi 330006, China; Jiangxi Key Laboratory of Molecular Diagnostics and Precision Medicine, Nanchang, Jiangxi 330006, China.
Int J Biochem Cell Biol. 2019 Oct;115:105591. doi: 10.1016/j.biocel.2019.105591. Epub 2019 Aug 20.
GATA-6 is a transcription factor that participates in cell lineage differentiation and organogenesis in many tissue types. The abnormal expression of GATA-6 is associated with the development of diverse cancers. GATA-6 acts as an oncogene or tumor suppressor based on tumor origin. Here, we investigated the effects of GATA-6 on lung squamous cell carcinoma (LSCC). We found that GATA-6 was significantly reduced in LSCC tissues compared with the paired normal tissues. The overexpression of GATA-6 inhibited LSCC cell proliferation and migration. Importantly, a luciferase reporter assay and chromatin immunoprecipitation assay demonstrated that GATA-6 negatively regulated the expression of sonic hedgehog (Shh) by directly binding to its promoter region. Furthermore, N-Shh stimulation rescued the inhibition of LSCC cell proliferation and migration upon GATA-6 overexpression. Thus, GATA-6 inhibited the proliferation and migration of LSCC cells by transcriptionally inhibiting the expression of Shh, indicating that targeting GATA-6 may be a potential approach for LSCC therapy.
GATA-6 是一种转录因子，参与多种组织类型的细胞谱系分化和器官发生。GATA-6 的异常表达与多种癌症的发生发展有关。GATA-6 根据肿瘤起源可作为癌基因或肿瘤抑制因子发挥作用。在这里，我们研究了 GATA-6 对肺鳞状细胞癌（LSCC）的影响。我们发现，与配对的正常组织相比，GATA-6 在 LSCC 组织中显著减少。GATA-6 的过表达抑制了 LSCC 细胞的增殖和迁移。重要的是，荧光素酶报告基因检测和染色质免疫沉淀实验表明，GATA-6 通过直接结合其启动子区域，负调控 sonic hedgehog（Shh）的表达。此外，N-Shh 刺激挽救了 GATA-6 过表达时对 LSCC 细胞增殖和迁移的抑制作用。因此，GATA-6 通过转录抑制 Shh 的表达抑制 LSCC 细胞的增殖和迁移，表明靶向 GATA-6 可能是 LSCC 治疗的一种潜在方法。
