期刊
MOLECULAR MEDICINE REPORTS
卷 10, 期 1, 页码 283-291出版社
SPANDIDOS PUBL LTD
DOI: 10.3892/mmr.2014.2144
关键词
miR-20a; colorectal cancer; epithelial-mesenchymal transition; metastasis; prognostic factor
资金
- Sichuan Provincial Education Department of China [CBY12-A-ZD16]
Accumulating evidence indicates that dysregulated microRNAs (miRNAs) are involved in cancer development, progression and metastasis. miR-20a was found to be involved in invasion and epithelial-mesenchymal transition (EMT) programs, with its aberrant expression having been observed in a variety of malignant tumors. However, the molecular mechanisms underlying the role of miR-20a in colorectal cancer (CRC) development remain to be fully elucidated. In the present study, the expression of miR-20a was compared between CRC tissue samples and the normal adjacent mucosa using quantitative polymerase chain reaction. The association of miR-20a 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 miR-20a precursor or a negative control miRNA precursor. The effect of miR-20a on the EMT in CRC cells in vitro was also analyzed. The regulatory effect of miR-20a on SMAD family member 4 (SMAD4) was evaluated using a dual-luciferase reporter assay. Relative expression levels of miR-20a were significantly higher in CRC tissue than those in the normal adjacent mucosa, and high expression of miR-20a correlated with lymph node metastases and distant metastases. Kaplan-Meier analysis indicated that patients with increased miR-20a levels exhibited unfavorable overall survival. Furthermore, multivariate analysis showed that miR-20a was an independent prognostic factor. The transfection of SW480 CRC cells with miR-20a promoted migration and invasion in vitro, and the upregulation of miR-20a induced EMT in CRC cells. An inverse correlation between the levels of miR-20a and SMAD4 was observed in patients with CRC. Overexpression of miR-20a in CRC cells decreased SMAD4 expression and decreased SMAD4-driven luciferase reporter activity. The present study revealed that miR-20a was an independent prognostic factor in CRC. Furthermore, miR-20a induced EMT and regulated migration and invasion of SW480 cells, at least in part via suppression of SMAD4 expression. The present study suggests that miR-20a may serve as a novel prognostic marker and therapeutic target for CRC.
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