miR-494 suppresses the progression of breast cancer in vitro by targeting CXCR4 through the Wnt/β-catenin signaling pathway

Abstract

Breast cancer is the most common cancer among women with a high mortality worldwide, which is mainly due to tumor invasion and metastasis. Previous studies have reported that microRNA-494 (miR-494) is downregulated in breast cancer cells. The present study investigated the role of miR-494 in the progression of breast cancer and the underlying mechanisms. The levels of miR-494 were analyzed in several breast cancer cell lines by quantitative reverse transcription PCR (qRT-PCR). The miR-494 mRNA levels were significantly lower in the malignant breast cancer cells than the level in the non-malignant normal breast epithelial cells. miR-494 mimic transfection upregulated the expression levels of E-cadherin, yet downregulated N-cadherin, vimentin and α-smooth muscle actin (α-SMA) in the breast cancer cells. As expected, the expression of these markers in breast cancer cells transfected with miR-494 inhibitors exhibited the opposite variation trend. MTT and Transwell assays showed that cell proliferation and invasion were both significantly suppressed by miR-494 mimics, and were significantly promoted by miR-494 inhibitors. The protein expression level of chemokine (C-X-C motif) receptor 4 (CXCR4) in the breast cancer cells was significantly inhibited by miR-494 mimics, and enhanced by miR-494 inhibitors. Yet, the mRNA level of CXCR4 was barely affected by miR-494 mimics or inhibitors. Dual-luciferase assay confirmed that miR-494 directly interacted with the 3′-untranslated region of CXCR4 mRNA by dual-luciferase assay. The miR-494 mimics also significantly inhibited the transcription levels of β-catenin, LEF1, CD44 and cyclin-D1, which was similar to the effect of siRNA targeted to CXCR4. In conclusion, miR-494 suppresses the progression of breast cancer through the Wnt/β-catenin signaling pathway, which is mediated by CXCR4.