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

Oncol Rep. 2015 Jul;34(1):525-31. doi: 10.3892/or.2015.3965. Epub 2015 May 8.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • In Vitro Techniques
  • MCF-7 Cells
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism*
  • Receptors, CXCR4 / genetics*
  • Receptors, CXCR4 / metabolism*
  • Wnt Signaling Pathway*


  • 3' Untranslated Regions
  • CXCR4 protein, human
  • MIRN494 microRNA, human
  • MicroRNAs
  • Receptors, CXCR4