Abstract
Several studies have shown the tumorigenesis role of transcriptional enhancer associate domain (TEAD) proteins; here, we initially explored expression, function and signalling mechanisms of TEAD4 in lung adenocarcinoma (LAD). Both the mRNA and protein levels of TEAD4 were increased in LAD tissues than those in adjacent nontumourous tissues. Besides, database search indicated a poorer clinical outcome in LAD patients with higher TEAD4 expression, revealing its potential tumour‐promoting role. Therefore, we conducted cellular experiments to further investigate its effect on tumour phenotypes. Accordingly, TEAD4 showed little impact on LAD cell cycle, proliferation, or apoptosis. However, silencing TEAD4 remarkably attenuated cell migration and invasion capacities. Consistently, several important epithelial‐mesenchymal transition (EMT) markers such as E‐cadherin and Slug were consequently altered by silencing TEAD4. Furthermore, we identified a novel TEAD4‐targeted microRNA, namely miR6839‐3p, and confirmed its function in suppressing TEAD4 expression. Finally, the impact of overexpressing miR6839‐3p mimics on LAD progression was validated, which showed a similar pattern with TEAD4 knockdown cells. Taken together, our data not only revealed the significant role of TEAD4 in promoting LAD progression and predicting clinical outcome but also distinguished miR6839‐3p mimics as a promising therapeutic direction.
Highlights
Lung cancer is one of the most prevalent malignant tumours with the highest growth rate of morbidity and mortality, currently is the leading cause of cancer-associated death and the greatest threat to human health.[1]
TEAD4 is located in both cytoplasm and nucleus; we separately evaluated the immunoreactivity in cytoplasm and nucleus
To better investigate the clinical significance of TEAD4 in non-small-cell lung cancer (NSCLC), we evaluated its prognostic effect via a public database of KaplanMeier plotter analysis
Summary
Lung cancer is one of the most prevalent malignant tumours with the highest growth rate of morbidity and mortality, currently is the leading cause of cancer-associated death and the greatest threat to human health.[1]. Despite significant advances in early detection and targeted therapies for lung cancer have been achieved, patients with advanced tumour stages (with distant metastasis) still end with poor clinical outcome. The evolutionarily conserved Hippo protein is initially identified as a key regulator in various biological processes including cell proliferation, cell contact inhibition, and cancer development.[5]. Activated LATS1/2 phosphorylate the YAP (YES-associated protein 1) and TAZ transcriptional coactivators. VGLL4 competes with YAP in binding to TEADs and suppresses lung cancer progression.[3]. The tumour regulating role of TEAD coactivators triggered us to explore expression and function of TEADs in lung cancer. The inhibitory effects of on TEAD4 signalling were confirmed in our study, which may help direct the targeted therapeutic strategy for LAD patients with high TEAD4 expression
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