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

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 χ 2 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.

Knockdown of TPT1-AS1 inhibits cell proliferation, cell cycle G1/S transition, and epithelial–mesenchymal transition in gastric cancer

“…Conversely, growth arrest associated lncRNA 1 (GASL1) has been reported to be significantly downregulated in GC tissues and to inhibit GC cell proliferation and tumor growth by inactivating the Wnt/β-catenin signaling pathway [13]. Emerging studies show that antisense lncRNAs (lncRNAs-AS) can modulate cancer progression by functioning as positive or negative regulators of coding genes [14][15][16][17]. Tumor protein translationally controlled 1 antisense RNA 1 (TPT1-AS1) has been studied by Jiang et al who showed that TPT1-AS1 as an oncogenic lncRNA promotes cell growth and metastasis in cervical cancer [18], as well as by Wu et al who further revealed that ectopic TPT1-AS1 expression is strongly associated with unfavorable epithelial ovarian cancer (EOC) clinicopathological features and induces EOC tumor growth and metastasis [19].…”

MAP3K4 kinase action and dual role in cancer

“…A recently discovered lncRNA, GATA binding protein 6 antisense (GATA6-AS), is downregulated in the tumor tissues of cervical squamous cell carcinoma patients. According to this study, MAP3K4 is downregulated when GATA6-AS is expressed, hindering cancer cells from migrating and invading [ 85 ]. With a similar mechanism, the long non-coding RNA-OIS1 inhibits HPV-positive, but not HPV-negative cervical squamous cell carcinoma by upregulating MAP3K4 [ 86 ].…”

Beyond MicroRNAs: Emerging Role of Other Non-Coding RNAs in HPV-Driven Cancers

“…Accordingly, OIS1 overexpression markedly reduced the proliferation of the HPV-positive SiHa cells, potentially by inhibiting the expression of the mitogen-activated protein kinase kinase kinase 4 (MTK-1) [90]. MTK-1 expression was also reduced following GATA binding protein 6 antisense (GATA6-AS) overexpression in CSCC cell lines; however, GATA6-AS expression levels were revealed to be significantly reduced in both HPV-positive and -negative CSCC patients, suggesting GATA6-AS might play a role in CSCC through an HPV-independent pathway [128]. The study of Wang et al, that was already discussed above, reported 19 lncRNAs that were differentially expressed between HPV-positive CSCC and adjacent non-tumor tissues, and the co-expression network and function prediction suggested that all of them could play a role in HPV-driven CSCC [100].…”