MicroRNA-200a suppresses the Wnt/β-catenin signaling pathway by interacting             with β-catenin.
The Wnt/β-catenin signaling pathway is crucial for human organ development             and is involved in tumor progression of many cancers. Accumulating evidence suggests             that the expression of β-catenin is, in part, regulated by specific microRNAs             (miRNAs). The purpose of this study was to determine the expression of a recently             identified epithelial to mesenchymal transition (EMT)-associated tumor suppressor             microRNA (miR)-200a, in cancer cells. We also aimed to identify specific miR-200a             target genes and to investigate the antitumor effects of miR-200a on the Wnt/β-catenin             signaling pathway. We employed TOP/FOP flash luciferase assays to identify the             effect of miR-200a on the Wnt/β-catenin pathway and we confirmed our observations             using fluorescence microscopy. To determine target genes of miR-200a, a 3' untranslated             region (3' UTR) luciferase assay was performed. Cell viability, invasion and wound             healing assays were carried out for functional analysis after miRNA transfection.             We further investigated the role of miR-200a in EMT by Western blot analysis.             We found fluctuation in the expression of miR-200a that was accompanied by changes             in the expression of members of the Wnt/β-catenin signaling pathway. We also determined             that miR-200a can directly interact with the 3' UTR of CTNNB1 (the gene that encodes             β-catenin) to suppress Wnt/β-catenin signaling. MiR-200a could also influence             the biological activities of SGC790 and U251 cells. Our results demonstrate that             miR-200a is a new tumor suppressor that can regulate the activity of the Wnt/β-catenin             signaling pathway via two mechanisms. MiR-200a is a candidate target for tumor             treatment via its regulation of the Wnt/β-catenin signaling pathway.
Department of Gastroenterology, Tianjin Medical University General Hospital, Heping District, Tianjin 300052, PR China.
Juan
J
Su
Anling
A
Zhang
Zhendong
Z
Shi
Feifei
F
Ma
Peiyu
P
Pu
Tao
T
Wang
Jie
J
Zhang
Chunsheng
C
Kang
Qingyu
Q
Zhang
D017209:Apoptosis / Q000235:genetics; D048708:Cell Growth Processes / Q000235:genetics; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection; D051153:Wnt Proteins / Q000235:genetics* / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000235:genetics*; D051176:beta Catenin / Q000235:genetics* / Q000378:metabolism
C495270:CTNNB1 protein, human; C533896:MIRN200 microRNA, human; D035683:MicroRNAs; D051153:Wnt Proteins; D051176:beta Catenin