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

Song,Lingqin; Liu,Di; Wang,Baofeng; He,Jianjun; Zhang,Shuqun; Dai,Zhijun; Ma,Xiaobin; Wang,Xijing

doi:10.3892/or.2015.3965

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

Authors:
- Lingqin Song
- Di Liu
- Baofeng Wang
- Jianjun He
- Shuqun Zhang
- Zhijun Dai
- Xiaobin Ma
- Xijing Wang
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Affiliations: Department of Oncology, The Second Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China, Department of Surgical Oncology, The First Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China
Published online on: May 8, 2015 https://doi.org/10.3892/or.2015.3965
Pages: 525-531

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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.

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