[Epithelial-mesenchymal transition (EMT) and its effect on microRNA expression in lung cancer].
OBJECTIVE
To investigate the effect of epithelial-mesenchymal transition (EMT) on the expression of microRNAs (miRNAs) in lung cancer A549 cells.


METHODS
Transforming growth factor beta-1 (TGF-beta 1) in different concentrations was used to induce EMT in lung cancer A549 cells. The morphological changes were observed under phase-contrast microscope. The changes of EMT-related proteins were analyzed by Western blot. The changes of miRNAs expression after EMT were detected by microRNA (miRNA) array. Real time quantitative RT-PCR was applied to verify the reliability of miRNA array results.


RESULTS
The lung cancer A549 cells became elongated and the cell-cell junction became loose after EMT. The epithelial protein marker E-cadherin was down-regulated and the mesenchymal protein markers vimentin and fibronectin up-regulated. There were 51 miRNAs showing statistically significant changes of expression more than double (P<0.05) after EMT. Among them 18 were up-regulated and 33 down-regulated. Of them, mir-33a was down-regulated by 92.8% and mir-193a-3p by 86.5%. Real time quantitative RT-PCR showed that mir-33a was down-regulated by 73.1% and mir-193a-3p by 56.6%.


CONCLUSIONS
Epithelial-mesenchymal transition has effects on the expression of miRNAs, and miRNAs may regulate the invasion and metastasis of lung cancer cells via EMT.
Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China.
Hai-Bing
HB
Wang
Hui-Jun
HJ
Zhang
Jin-Mei
JM
Su
Wen-Yong
WY
Zhou
He-Yong
HY
Wang
Xiao-Feng
XF
Chen
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D015820:Cadherins / Q000378:metabolism; D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D005353:Fibronectins / Q000378:metabolism; D020869:Gene Expression Profiling; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000008:administration & dosage / Q000494:pharmacology; D014746:Vimentin / Q000378:metabolism
D015820:Cadherins; D005353:Fibronectins; C546818:MIRN193 microRNA, human; C550416:MIRN33a microRNA, human; D035683:MicroRNAs; D053773:Transforming Growth Factor beta1; D014746:Vimentin