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Mir-186-5p Regulates WNT Signaling Pathway by Targeting TCF4 Transcription Factor
Author(s) -
Zahra Safavi Bayat,
Bahram Mohammad Soltani
Publication year - 2018
Publication title -
journal of molecular biology research
Language(s) - English
Resource type - Journals
eISSN - 1925-4318
pISSN - 1925-430X
DOI - 10.5539/jmbr.v8n1p130
Subject(s) - wnt signaling pathway , tcf4 , biology , cell cycle , microrna , signal transduction , microbiology and biotechnology , transcription factor , lrp6 , lrp5 , cell culture , cell , cancer research , gene , genetics , enhancer
The evolutionarily conserved Wnt signaling pathway plays essential roles during embryonic development, tissue homeostasis and differentiation. This pathway is deregulated in many cancers especially colorectal cancer. MiRNAs are a class of small noncoding RNAs that may play a major role in post transcriptional regulation of many genes and signaling pathway such as WNT signaling pathway. Here, we intended to investigate if miR-186-5p is capable of regulating WNT signaling pathway wia suppression TCF4 gene expression. miR-186-5p was bioinformatically predicted as a candidate regulator of TCF4 gene expression and then, in this experimental study, miR-186-5p was overexpressed in SW480 cell line and its increased expression was detected through quantitative reverse transcription polymerase chain reaction (RT-qPCR). The effect of miR-186-5p on WNT pathway was analysied with TOP/FOP flash assay in SW480 cell line. Finally, flow cytometery was used to inves tigate the effect of miR-186-5p overexpression on cell cycle progression in SW480 cell line. miR-186-5p was overexpressed in the SW480 cell line and its overexpression resulted in significant reduction of the TCF4 mRNA level. TOP/FOP flash assay, confirmed the negative effect of miR-186-5p on the Wnt pathway in SW480 cells. Finally, Overexpression of miR186-5p in SW480 cells resulted in cell cycle arrest in subG1 phase, detected by flow cytometry. Overall, accumulative results indi-cated that miR-186-5p by targeting TCF4 is potentially one of the regulators of the WNT signaling pathway.

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