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MircoRNA-33a inhibits epithelial-to-mesenchymal transition and metastasis and
could be a prognostic marker in non-small cell lung cancer
#MMPMID26330060
Yang L
; Yang J
; Li J
; Shen X
; Le Y
; Zhou C
; Wang S
; Zhang S
; Xu D
; Gong Z
Sci Rep
2015[Sep]; 5
(?): 13677
PMID26330060
show ga
Understanding the molecular mechanism by which epithelial mesenchymal transition
(EMT)-mediated cancer metastasis and how microRNA (miRNA) regulates lung cancer
progression via Twist1-activated EMT may provide potential therapeutic targets
for cancer therapy. Here we found that miR-33a, an intronic miRNA located within
the sterol regulatory element-binding protein 2 (SREBP-2) gene, is expressed at
low levels in metastatic non-small cell lung cancer (NSCLC) cells and is
inversely correlated with Twist1 expression. Conversely, miR-33a knockdown
induces EMT and miR-33a overexpression blocks EMT by regulating of Twist1
expression in NSCLC cells. Bioinformatical prediction and luciferase reporter
assay confirm that Twist1 is a direct target of miR-33a. Additionally, Twist1
knockdown blocks EMT-related metastasis and forced expression of miR-33a inhibits
lung cancer metastasis in a xenograft animal model. Clinically, miR-33a is found
to be at low levels in NSCLC patients and down-regulation of miR-33a predicts a
poor prognosis. These findings suggest that miR-33a targets Twist1 and inhibits
invasion and metastasis in NSCLC. Thus, miR-33a might be a potential prognostic
marker and of therapeutic relevance for NSCLC metastasis intervention.
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