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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
2017 ; 7
(3
): 628-646
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miR-495 promotes the chemoresistance of SCLC through the epithelial-mesenchymal
transition via Etk/BMX
#MMPMID28401017
Wei T
; Zhu W
; Fang S
; Zeng X
; Huang J
; Yang J
; Zhang J
; Guo L
Am J Cancer Res
2017[]; 7
(3
): 628-646
PMID28401017
show ga
miR-495 serves as an oncogenic miRNA or a tumor suppressor in different types of
cancer. However, its role in the drug resistance of small cell lung cancer (SCLC)
remains unidentified. In this study, we investigated whether miR-495 regulates
the chemoresistance of SCLC through the epithelial-mesenchymal transition (EMT)
via Epithelial and endothelial tyrosine kinase (Etk/BMX) using two drug-resistant
cell lines. Loss- and gain-of-function experiments showed miR-495 regulated cell
proliferation, tumor growth and drug resistance. miR-495 suppression or Etk/BMX
elevation in SCLC specimens was correlated with poor pathologic stage and
survival time. Etk/BMX was one of the directly targeted genes of miR-495. Ectopic
expression of Etk/BMX obviously rescued the miR-495 elevation elevation-induced
inhibition of drug resistance. Etk/BMX over-expression led to higher levels of
EMT mesenchymal factors (Zeb-2, Twist, Vim) and lower levels of the epithelial
molecule ?-catenin, while suppression of Etk/BMX showed the opposite trend.
Knockdown of Zeb-2 and Twist inhibited the chemoresistance of cells. Our study
revealed that miR-495 promoted the chemoresistance of SCLC through the
epithelial-mesenchymal transition via Etk/BMX. miR-495 re-expression or Etk/BMX
depletion is a promising strategy for interfering with chemoresistance in SCLC.