title: CXCR4 3'UTR functions as a ceRNA in promoting metastasis, proliferation and survival of MCF-7 cells by regulating miR-146a activity.
abstract: CXCR4 is the most common chemokine receptor expressed on tumor cells, and it is closely correlated with cancer cell stemness. This study was carried out to explore whether CXCR4 could function as a competitive endogenous RNA to promote metastasis, proliferation and survival in MCF-7 breast cancer cells. We validated that CXCR4, together with TRAF6 and EGFR, was directly targeted by miR-146a in MCF-7 cells. Overexpression of CXCR4 3'UTR inhibited the activity of miR-146a, thus elevating the expression of CXCR4, TRAF6 and EGFR. These oncoproteins further activated NF-κB pathway and promoted the proliferation, migration, invasion and anti-apoptotic activity of MCF-7 cells. Collectively, our study provided new insights into the function of CXCR4 in breast cancer: it promotes tumor progression as both a protein-coding gene and a non-coding RNA, complicating the mechanism by which oncogenes promote tumor progression.
authors.affiliation: School of Life Science and Technology, China Pharmaceutical University, #24 Tongjiaxiang, Nanjing 210009, China; Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, #24 Tongjiaxiang, Nanjing 210009, China.
authors.forename: Tianjing
authors.initials: T
authors.lastname: Zheng
authors.affiliation: School of Life Science and Technology, China Pharmaceutical University, #24 Tongjiaxiang, Nanjing 210009, China; Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, #24 Tongjiaxiang, Nanjing 210009, China.
authors.forename: Jinjiang
authors.initials: J
authors.lastname: Chou
authors.affiliation: School of Life Science and Technology, China Pharmaceutical University, #24 Tongjiaxiang, Nanjing 210009, China; Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, #24 Tongjiaxiang, Nanjing 210009, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
authors.affiliation: School of Life Science and Technology, China Pharmaceutical University, #24 Tongjiaxiang, Nanjing 210009, China; State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, #24 Tongjiaxiang, Nanjing 210009, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Medical college of Yangzhou University, #11, Huaihailu Road, Yangzhou, China.
authors.forename: Haiwei
authors.initials: H
authors.lastname: Ni
authors.affiliation: School of Life Science and Technology, China Pharmaceutical University, #24 Tongjiaxiang, Nanjing 210009, China; Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, #24 Tongjiaxiang, Nanjing 210009, China.
authors.forename: Xiaoman
authors.initials: X
authors.lastname: Li
authors.affiliation: School of Life Science and Technology, China Pharmaceutical University, #24 Tongjiaxiang, Nanjing 210009, China; Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, #24 Tongjiaxiang, Nanjing 210009, China.
authors.forename: Lufeng
authors.initials: L
authors.lastname: Zheng
authors.affiliation: School of Life Science and Technology, China Pharmaceutical University, #24 Tongjiaxiang, Nanjing 210009, China; Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, #24 Tongjiaxiang, Nanjing 210009, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Tang
authors.affiliation: School of Life Science and Technology, China Pharmaceutical University, #24 Tongjiaxiang, Nanjing 210009, China; State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, #24 Tongjiaxiang, Nanjing 210009, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Jin
authors.affiliation: School of Life Science and Technology, China Pharmaceutical University, #24 Tongjiaxiang, Nanjing 210009, China; Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, #24 Tongjiaxiang, Nanjing 210009, China. Electronic address: xitao18@hotmail.com.
authors.forename: Tao
authors.initials: T
authors.lastname: Xi
mesh_terms: D020413:3' Untranslated Regions; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D035683:MicroRNAs / Q000235:genetics / Q000502:physiology*; D016328:NF-kappa B / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000235:genetics*; D009362:Neoplasm Metastasis; D015513:Oncogene Proteins / Q000502:physiology*; D019718:Receptors, CXCR4 / Q000235:genetics*; D048029:TNF Receptor-Associated Factor 6 / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; C527276:CXCR4 protein, human; C542542:MIRN146 microRNA, human; D035683:MicroRNAs; D016328:NF-kappa B; D015513:Oncogene Proteins; D019718:Receptors, CXCR4; D048029:TNF Receptor-Associated Factor 6; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: Breast cancer; CXCR4 3′UTR; Competitive endogenous RNA; EGFR; TRAF6; miR-146a