miR‑20a is an independent prognostic factor in colorectal cancer and is involved in cell metastasis

Zhang,Guang‑Jun; Li,Yu; Zhou,He; Xiao,Hua‑Xu; Zhou,Tong

doi:10.3892/mmr.2014.2144

miR‑20a is an independent prognostic factor in colorectal cancer and is involved in cell metastasis

Authors:
- Guang‑Jun Zhang
- Yu Li
- He Zhou
- Hua‑Xu Xiao
- Tong Zhou
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Affiliations: The First Department of General Surgery, Institute of Hepato‑Biliary‑Pancreas and Intestinal Disease, The Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan 637000, P.R. China
Published online on: April 15, 2014 https://doi.org/10.3892/mmr.2014.2144
Pages: 283-291

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Abstract

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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