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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 J+Exp+Clin+Cancer+Res
2016 ; 35
(1
): 132
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MiR-137 and miR-34a directly target Snail and inhibit EMT, invasion and
sphere-forming ability of ovarian cancer cells
#MMPMID27596137
Dong P
; Xiong Y
; Watari H
; Hanley SJ
; Konno Y
; Ihira K
; Yamada T
; Kudo M
; Yue J
; Sakuragi N
J Exp Clin Cancer Res
2016[Sep]; 35
(1
): 132
PMID27596137
show ga
BACKGROUND: In ovarian cancer (OC) cells, Snail was reported to induce the
epithelial-to-mesenchymal transition (EMT), which is a critical step in OC
metastasis. At present little is known about controlling Snail expression in OC
cells by using specific microRNAs (miRNAs). METHODS: We first used a
computational target prediction analysis to identify 6 candidate miRNAs that bind
to the 3'-untranslated region (3'-UTR) region of the Snail mRNA. Among these
miRNAs, two miRNAs (miR-137 and miR-34a) with a potential to regulate Snail were
validated by quantitative real-time PCR, Western blot analysis, and Snail 3'-UTR
reporter assays. We assessed the effects of miR-137 and miR-34a on EMT, invasion
and sphere formation in OC cells. We also evaluated the expression of miR-137 and
miR-34a in OC tissues and adjacent normal tissues and analyzed the relationship
between their expression and patient survival. RESULTS: We report that OC tissues
possess significantly decreased levels of miR-137 and miR-34a and increased
expression of Snail when compared to their adjacent normal tissues, and lower
miR-137 and miR-34a expression correlates with worse patient survival. Using
luciferase constructs containing the 3'-UTR region of Snail mRNA combined with
miRNA overexpression and mutagenesis, we identified miR-137 and miR-34a as direct
suppressors of Snail in OC cells. The introduction of miR-137 and miR-34a
resulted in the suppression of Snail at both the transcript and protein levels,
and effectively suppressed the EMT phenotype and sphere formation of OC cells.
However, the inhibition of miR-137 and miR-34a with antisense oligonucleotides
promoted EMT and OC cell invasion. Moreover, ectopic expression of Snail
significantly reversed the inhibitory effects of miR-137 and miR-34a on OC cell
invasion and sphere formation. CONCLUSIONS: These findings suggest that both
miR-137 and miR-34a act as Snail suppressors to negatively regulate EMT, invasive
and sphere-forming properties of OC cells.