MicroRNA-23a regulates epithelial-to-mesenchymal transition in endometrial endometrioid adenocarcinoma by targeting SMAD3.
BACKGROUND
To investigate the role of total cellular microRNA (miRNA) in regulating epithelial-to-mesenchymal transition (EMT) during human endometrial endometrioid adenocarcinoma (EEC).


METHODS
A miRCURY LNA microRNA array was used to evaluate the miRNA profiles of human EEC tissues and corresponding nontumorous endometriums. An in vitro model of TGF-β induced EMT in HEC-1-A cells was used to investigate the role of miRNAs in the EEC during EMT. The expression of SMAD3, SMAD5, and a panel of EMT markers was detected by Western blot and quantitative PCR.


RESULTS
The results of miRNA profiling in human EEC tissues and corresponding nontumorous endometriums demonstrated that miR-23a expression was down-regulated. Using bioinformatics, we identified SMAD3 or SMAD5 maybe as a predicted target of miR-23a. The results of luciferase reporter assay showed miR-23a directly targets and down-regulates human SMAD3 protein levels, not SMAD5 protein levels. Furthermore, overexpression of miR-23a in HEC-1-A cells increased E-cadherin expression and decreased the expression of vimentin and alpha smooth muscle actin, markers of mesenchymal cellular phenotype.


CONCLUSIONS
Our data provide firm evidence of a role for miR-23a in the direct regulation of EMT through its targeting of SMAD3. Due to its ability to repress the EMT, miR-23a may be a novel target for EER therapeutic intervention.
Gynecology Department, Changning Maternity and Infant Health Hospital, No. 773, Wuyi Road, Changning District, Shanghai, 200051 China.
Ping
P
Liu
Gynecology Department, Changning Maternity and Infant Health Hospital, No. 773, Wuyi Road, Changning District, Shanghai, 200051 China.
Chao
C
Wang
Gynecology Department, Changning Maternity and Infant Health Hospital, No. 773, Wuyi Road, Changning District, Shanghai, 200051 China.
Chengbin
C
Ma
Gynecology Department, Changning Maternity and Infant Health Hospital, No. 773, Wuyi Road, Changning District, Shanghai, 200051 China.
Qiongwei
Q
Wu
Gynecology Department, Changning Maternity and Infant Health Hospital, No. 773, Wuyi Road, Changning District, Shanghai, 200051 China.
Wenying
W
Zhang
Gynecology Department, Changning Maternity and Infant Health Hospital, No. 773, Wuyi Road, Changning District, Shanghai, 200051 China.
Guoying
G
Lao
Endometrial endometrioid adenocarcinoma; Epithelial-to-mesenchymal transition; MicroRNA; SMAD3