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2017 ; 17
(ä): 36
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miR-484 suppresses proliferation and epithelial-mesenchymal transition by
targeting ZEB1 and SMAD2 in cervical cancer cells
#MMPMID28286418
Hu Y
; Xie H
; Liu Y
; Liu W
; Liu M
; Tang H
Cancer Cell Int
2017[]; 17
(ä): 36
PMID28286418
show ga
BACKGROUND: MicroRNAs (miRNAs) play important roles in cancer initiation and
development. Epithelial-mesenchymal transition (EMT) is a form of cellular
plasticity that is critical for embryonic development and metastasis. The purpose
of the study was to determine the function and mechanism of miR-484 in initiation
and development of cervical cancer (CC). METHODS: We determined the expression
levels of miR-484 in cervical cancer tissues and cell lines with RT-qPCR.
Prediction algorithms and EGFP reporter assay were performed to evaluate the
targets for miR-484. MTT assay, colony formation assay, flow cytometric analysis,
transwell cell migration and invasion assays, and detection of EMT markers were
employed to investigate the roles of miR-484 and the targets in regulation of
cell proliferation and EMT process. We also used rescue experiments to confirm
the effect of miR-484 on CC cells through directly regulating the expression of
its targets. RESULTS: Firstly we found miR-484 was down-regulated in cervical
cancer tissues and cell lines compared with their matched non-cancerous tissues
or normal cervical keratinocytes cells. Further studies revealed that
overexpression of miR-484 suppressed the cell proliferation, while exacerbates
apoptosis. Besides, miR-484 suppressed cellular migration, invasion and EMT
process of CC cells. EGFP reporter assay showed that miR-484 binds to ZEB1 and
SMAD2 3'UTR region and reduced their expression. The expression of miR-484 had
reverse correlation with SMAD2/ZEB1, and SMAD2/ZEB1 had positive correlation with
each other in cervical cancer tissues and cell lines. Furthermore, the ectopic
expression of ZEB1 or SMAD2 could rescue the malignancies suppressed by miR-484,
suggesting that miR-484 down-regulates ZEB1 and SMAD2 to repress tumorigenic
activities. CONCLUSION: We found miR-484 inhibits cell proliferation and the EMT
process by targeting both ZEB1 and SMAD2 genes and functions as a tumor
suppressor, which may served as potential biomarkers for cervical cancer.