GATA-6 transcriptionally inhibits Shh to repress cell proliferation and migration in lung squamous cell carcinoma

被引:8
作者
Xu, Linlin [1 ,3 ]
Deng, Suyue [1 ,3 ]
Xiong, Huanting [1 ,2 ,3 ]
Shi, Wei [1 ,2 ,3 ]
Luo, Shiwen [1 ,3 ]
Chen, Limin [1 ,3 ]
机构
[1] Nanchang Univ, Affiliated Hosp 1, Ctr Expt Med, Nanchang 330006, Jiangxi, Peoples R China
[2] Nanchang Univ, Sch Pharm, Nanchang 330006, Jiangxi, Peoples R China
[3] Jiangxi Key Lab Mol Diagnost & Precis Med, Nanchang 330006, Jiangxi, Peoples R China
基金
中国国家自然科学基金;
关键词
GATA-6; Sonic hedgehog (Shh); Lung squamous carcinoma (LSCC); Proliferation; Migration; HEDGEHOG; CANCER; GENES; SUPPRESSOR; EXPRESSION; INVASION; BIOLOGY;
D O I
10.1016/j.biocel.2019.105591
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页数:8
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