406982

MIR20A

Accumulating evidence indicates that dysregulated microRNAs (miRNAs) are involved in cancer development, progression and metastasis. miR20a was found to be involved in invasion and epithelialmesenchymal transition (EMT) programs, with its aberrant expression having been observed in a variety of malignant tumors. However, the molecular mechanisms underlying the role of miR20a in colorectal cancer (CRC) development remain to be fully elucidated. In the present study, the expression of miR20a was compared between CRC tissue samples and the normal adjacent mucosa using quantitative polymerase chain reaction. The association of miR20a expression with clinicopathological characteristics was assessed using appropriate statistical analysis. The migration and invasion of SW480 cells was examined following transfection of the cells with either miR20a precursor or a negative control miRNA precursor. The effect of miR20a on the EMT in CRC cells in vitro was also analyzed. The regulatory effect of miR20a on SMAD family member 4 (SMAD4) was evaluated using a dualluciferase reporter assay. Relative expression levels of miR20a were significantly higher in CRC tissue than those in the normal adjacent mucosa, and high expression of miR20a correlated with lymph node metastases and distant metastases. KaplanMeier analysis indicated that patients with increased miR20a levels exhibited unfavorable overall survival. Furthermore, multivariate analysis showed that miR20a was an independent prognostic factor. The transfection of SW480 CRC cells with miR20a promoted migration and invasion in vitro, and the upregulation of miR20a induced EMT in CRC cells. An inverse correlation between the levels of miR20a and SMAD4 was observed in patients with CRC. Overexpression of miR20a in CRC cells decreased SMAD4 expression and decreased SMAD4driven luciferase reporter activity. The present study revealed that miR20a was an independent prognostic factor in CRC. Furthermore, miR20a induced EMT and regulated migration and invasion of SW480 cells, at least in part via suppression of SMAD4 expression. The present study suggests that miR20a may serve as a novel prognostic marker and therapeutic target for CRC.

Messenchymal to epithelial transition (MET) is a significant physiological phenomenon involved in embryogenesis and cancer. This study aims at investigating the mechanism of microRNA-20a (miR-20a) mediated regulation of mesenchymal to epithelial transition and identification of its direct target genes in breast cancer cell-line, MDA-MB-231. Reduced migratory and invasive property, altered cellular morphology along with reduced capability for attachment to basement membrane was acquired by over-expression of miR-20a in invasive MDA-MB-231 cell-line initially expressing low level of this micro-RNA, indicating direct correlation between abundance of miR-20a and metastatic property. The switch from mesenchymal to epithelial cells mediated by miR-20a involved post-transcriptional down-regulation of twist1, which in turn controls downstream epithelial markers like E-cadherin, claudin and mesenchymal markers like N-cadherin, fibronectin, the crucial players of mesenchymal to epithelial transition (MET). Furthermore, another key component, TGF-beta and one of its receptors (TGFBR2) were found to be down-regulated by miR-20a. Additionally, reporter assay established that post-transcriptional down-regulation of TGFBR2 occurred through direct binding of miR-20a to its 3'UTR, thus abrogating the TGF-beta signaling pathway resulting in inhibition of MET. Delineating the underlying molecular mechanism of miR-20a-mediated MET and defining the target genes will help us to introduce a miRNA-mediated effective therapeutic strategy against breast cancer.CI - Copyright (c) 2017 Elsevier Inc. All rights reserved.