Upregulation of lncRNA GATA6-AS suppresses the migration and invasion of cervical squamous cell carcinoma by downregulating MTK-1

Oncol Lett. 2019 Sep;18(3):2605-2611. doi: 10.3892/ol.2019.10554. Epub 2019 Jul 4.

Abstract

The diagnosis and treatment of cervical squamous cell carcinoma is challenged by difficulties in the determination of tumor invasion. GATA binding protein 6 antisense (GATA6-AS) is a recently identified long non-coding RNA that exhibits critical functions in the growth of endothelial cells; however, to the best of our knowledge, its involvement in other physiological and pathological processes is unknown. By reverse transcription-quantitative polymerase chain reaction, the present study examined the expression of GATA6-AS in tumor tissues and adjacent healthy tissues, and the serum from patients with cervical squamous cell carcinoma and healthy controls. The diagnostic and prognostic potentials of GATA6-AS for cervical squamous cell carcinoma were analyzed by receiver operating characteristic curve analysis and survival curve analysis, respectively. Associations between the serum levels of GATA6-AS and clinical characteristics of patients with cervical squamous cell carcinoma were analyzed by a χ2 test. A GATA6-AS overexpression vector was transfected into cervical squamous cell carcinoma cells, and the effects on cell migration and invasion were investigated by Transwell migration and invasion assays, respectively. The expression of mitogen-activated protein kinase kinase 4 (MTK-1) following transfection with the GATA6-AS overexpression vector was detected by western blot analysis. It was identified that the expression levels of GATA6-AS were lower in tumor tissues compared with healthy tissues. In addition, serum levels of GATA6-AS were higher in patients compared with healthy controls. The serum levels of GATA6-AS were associated with tumor metastasis, and may serve as a potential diagnostic and prognostic marker for cervical squamous cell carcinoma. Furthermore, GATA6-AS overexpression inhibited cancer cell migration and invasion. The expression levels of MTK-1 were also reduced following GATA6-AS overexpression. Therefore, the present study proposed that downregulated GATA6-AS expression was associated with tumor metastasis in cervical squamous cell carcinoma, and that GATA6-AS expression may inhibit cancer cell migration and invasion by downregulating MTK-1.

Keywords: cervical squamous cell carcinoma; invasion; long non-coding RNA GATA binding protein 6 antisense; migration; mitogen-activated protein kinase kinase 4.