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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Am+J+Cancer+Res
2015 ; 5
(3
): 1158-68
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miR-222/VGLL4/YAP-TEAD1 regulatory loop promotes proliferation and invasion of
gastric cancer cells
#MMPMID26045994
Li N
; Yu N
; Wang J
; Xi H
; Lu W
; Xu H
; Deng M
; Zheng G
; Liu H
Am J Cancer Res
2015[]; 5
(3
): 1158-68
PMID26045994
show ga
Gastric cancer (GC) is one of the most common malignant tumors and recent data
demonstrates the tumor suppressor role of VGLL4 in GC, but the mechanisms for
VGLL4 downregulation in GC remain to be elucidated. Here, we confirmed the
suppressor role of VGLL4 on proliferation and invasion in GC cells with
over-activated YAP-TEAD signal, and indicated the reverse correlation between
expression patters of VGLL4 and miR-222. Bioinformatics analysis combined with
experimental confirmation revealed VGLL4 is a direct target of miR-222 in GC
cells. Functionally, miR-222 inhibitor significantly inhibited GC cells
proliferation and invasion and VGLL4 knockdown abolished the effects of miR-222
inhibitor. Moreover, TEAD1 knockdown resulted in decrease of miR-222 expression
and increase of VGLL4 expression, and also resulted in reduction of luciferase
activity driven by miR-222 promoter in GC cells, suggesting over-activated TEAD1
positively feedback transcriptionally regulates miR-222 expression via physically
binding to the miR-222 promoter indicated by ChIP assay. Collectively, our
findings implied the important role of miR-222/VGLL4/YAP-TEAD1 regulatory loop
maintaining over-activated YAP-TEAD1 signal in GC cells, and enriched the
rationale of VGLL4 in GC based on which a promising therapeutic strategy will be
developed.