MiRNA-802 inhibits the metastasis of colorectal cancer by targeting FOXE1

Y. Zhang, L.-N. Ma, Y. Xie

Department of Traditional Chinese Medicine, Shanxi Cancer Hospital, Taiyuan, China. 219zhangyong@sina.com

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• Oncology

OBJECTIVE: The aim of this study was to explore the role of microRNA-802 (miRNA-802) in the progression of colorectal cancer (CRC) and the underlying mechanism.

PATIENTS AND METHODS: The relative expression levels of miRNA-802 and FOXE1 in 40 paired CRC tissues and adjacent normal tissues were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The correlation between miRNA-802 expression and the pathological indexes of CRC patients was assessed. Meanwhile, the prognostic potentials of miRNA-802 and FOXE1 in CRC patients were identified through the Kaplan-Meier method. After overexpression of miRNA-802, the changes in the proliferative, migratory, and invasive capacities of HT29 and HCT-8 cells were evaluated in vitro. The Dual-Luciferase Reporter Gene Assay was applied to investigate the binding relationship between miRNA-802 and FOXE1. Finally, the rescue experiments were carried out to uncover the role of the miRNA-802/FOXE1 axis in regulating the cellular behaviors of CRC.

RESULTS: MiRNA-802 was significantly downregulated in CRC tissues and cell lines. CRC patients with a low level of miRNA-802 had significantly higher rates of lymphatic metastasis and distant metastasis, as well as worse overall survival. The transfection of miRNA-802 mimics remarkably attenuated the proliferation, migration, and invasion of HT29 and HCT-8 cells. FOXE1 expression was significantly upregulated in CRC tissues and cell lines. Meanwhile, the expression of FOXE1 was negatively correlated with miRNA-802 in CRC tissues. A higher level of FOXE1 indicated the worse prognosis of CRC patients. The Dual-Luciferase Reporter Gene Assay further verified the binding relationship between FOXE1 and miRNA-802. Importantly, the overexpression of FOXE1 could reverse the regulatory effects of miRNA-802 on the cellular behaviors of CRC.

CONCLUSIONS: MiRNA-802 is significantly downregulated in CRC, and is closely related to lymphatic and distant metastasis of CRC. Furthermore, miRNA-802 alleviates the malignant progression of CRC via negatively regulating FOXE1.

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