title: Upregulation of microRNA-181b inhibits CCL18-induced breast cancer cell metastasis and invasion via the NF-κB signaling pathway.
abstract: The purpose of the present study was to investigate the effects of upregulating microRNA (miR)-181b expression in tumor-associated macrophages regarding breast cancer cell metastasis and to identify the target gene. Ectopic miR-181b was transfected into MDA-MB-231 and MCF-7 breast cancer cell lines with or without chemokine ligand 18 (CCL18) stimulation. Cell proliferation, migration/invasion and apoptosis rate were investigated. The binding effects of miR-181b to the 3'-untranslated region (UTR) of the nuclear factor (NF)-κB gene were detected with the dual luciferase reporter system. Immunofluorescent staining of the NF-κB key component P65 was performed. The messenger (m) RNA and protein expression of NF-κB induced by CCL18 with or without miR-181b stimulation was evaluated with reverse transcription-quantitative polymerase chain reaction and western blot analysis. When compared with the CCL18-stimulated group, miR-181b mimic-transfected cells exhibited significantly inhibited proliferation and migration, with an increased cell apoptosis percentage in a dose-dependent manner. Furthermore, the luciferase activity was reduced for cells with NF-κB 3'-UTR wild-type that were co-transfected with miR-181b mimics. Immunofluorescent staining of NF-κB demonstrably weakened the P65 signal in stimulated miR-181b mimic cells when compared with parental and CCL18-treated cells. The increased expression level of NF-κB induced by CCL18 in MDA-MB-231 and MCF-7 cells was suppressed by miR-181b mimics. Overexpression of miR-181b suppressed cell survival rate and migration. This overexpression may achieve this goal by regulating the NF-κB pathway in breast cancer cells. Our study demonstrated a potential therapeutic application of miR-181b in the treatment of breast cancer.
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan 453100, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Pathophysiology, Xinxiang Medical University, Xinxiang, Henan 453003, P.R. China.
authors.forename: Yu-Xia
authors.initials: YX
authors.lastname: Wang
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan 453100, P.R. China.
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Chen
authors.affiliation: Department of Physiology, Xinxiang Medical University, Xinxiang, Henan 453003, P.R. China.
authors.forename: Ming-Li
authors.initials: ML
authors.lastname: Ji
keywords: apoptosis; breast cancer cell; chemokine ligand 18; microRNAs; migration