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2018 ; 9
(20
): 15198-15207
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miR-145 expression enhances integrin expression in SK-GT-4 cell line by
down-regulating c-Myc expression
#MMPMID29632636
Derouet MF
; Dakpo E
; Wu L
; Zehong G
; Conner J
; Keshavjee S
; de Perrot M
; Waddell T
; Elimova E
; Yeung J
; Darling GE
Oncotarget
2018[Mar]; 9
(20
): 15198-15207
PMID29632636
show ga
Adenocarcinoma of the esophagus is increasing in frequency and is the 6th most
common cause of cancer death in North America. In adenocarcinoma cell lines, we
have previously demonstrated that expression of miR-145, leads to enhanced
invasion, resistance to anoikis and better attachment to fibronectin in
esophageal adenocarcinoma. In contrast, expression of miR-145 acts as a tumor
suppressor in squamous cell carcinoma. The molecular mechanisms responsible for
the oncogenic effects of miR-145 were investigated. In this report, we
demonstrate that we can partially recreate the miR-145 effects in EAC by knock
down of the expression of c-Myc, which is one of the targets of miR-145. Knocking
down of c-Myc expression resulted in upregulation of integrin subunits ?5 and ?3.
Finally, we demonstrated that integrin ?5 expression correlates to fibronectin
attachment potential whereas integrin ?3 expression correlates with resistance to
anoikis and invasion potential. Finally, we demonstrate that expression of
miR-145 in esophageal adenocarcinoma cell line (SK-GT-4) enhances tumor growth
and metastasis in a NOD/SCID xenograft model. Overall, the oncogenic potential of
miR-145 in EAC appears to be mediated by downregulation of c-Myc leading to the
expression of integrins subunits ?5 and ?3.