title: 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.
authors.affiliation: Department of Oncology, The Second Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
authors.forename: Lingqin
authors.initials: L
authors.lastname: Song
authors.affiliation: Department of Oncology, The Second Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
authors.forename: Di
authors.initials: D
authors.lastname: Liu
authors.affiliation: Department of Oncology, The Second Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
authors.forename: Baofeng
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Surgical Oncology, The First Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Jianjun
authors.initials: J
authors.lastname: He
authors.affiliation: Department of Oncology, The Second Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
authors.forename: Shuqun
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Oncology, The Second Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Dai
authors.affiliation: Department of Oncology, The Second Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
authors.forename: Xiaobin
authors.initials: X
authors.lastname: Ma
authors.affiliation: Department of Oncology, The Second Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
authors.forename: Xijing
authors.initials: X
authors.lastname: Wang
mesh_terms: D020413:3' Untranslated Regions; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D066298:In Vitro Techniques; D061986:MCF-7 Cells; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000235:genetics* / Q000378:metabolism*; D060449:Wnt Signaling Pathway
chemical_list: D020413:3' Untranslated Regions; C527276:CXCR4 protein, human; C547168:MIRN494 microRNA, human; D035683:MicroRNAs; D019718:Receptors, CXCR4