TEAD4 exerts pro-metastatic effects and is negatively regulated by miR6839-3p in
lung adenocarcinoma progression
#MMPMID29667772
Zhang Q
; Fan H
; Zou Q
; Liu H
; Wan B
; Zhu S
; Hu Y
; Li H
; Zhang C
; Zhou L
; Zhu Q
; Xiao K
; Zhang J
; Zhan P
; Lv T
; Song Y
J Cell Mol Med
2018[Jul]; 22
(7
): 3560-3571
PMID29667772
show ga
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.
|Adenocarcinoma of Lung/genetics/mortality/*pathology
[MESH]
free
free
free
