title: miR-671-5p inhibits epithelial-to-mesenchymal transition by downregulating FOXM1 expression in breast cancer.
abstract: MicroRNA (miRNA) dysfunction is associated with a variety of human diseases, including cancer. Our previous study showed that miR-671-5p was deregulated throughout breast cancer progression. Here, we report for the first time that miR-671-5p is a tumor-suppressor miRNA in breast tumorigenesis. We found that expression of miR-671-5p was decreased significantly in invasive ductal carcinoma (IDC) compared to normal in microdissected formalin-fixed, paraffin-embedded (FFPE) tissues. Forkhead Box M1 (FOXM1), an oncogenic transcription factor, was predicted as one of the direct targets of miR-671-5p, which was subsequently confirmed by luciferase assays. Forced expression of miR-671-5p in breast cancer cell lines downregulated FOXM1 expression, and attenuated the proliferation and invasion in breast cancer cell lines. Notably, overexpression of miR-671-5p resulted in a shift from epithelial-to-mesenchymal transition (EMT) to mesenchymal-to-epithelial transition (MET) phenotypes in MDA-MB-231 breast cancer cells and induced S-phase arrest. Moreover, miR-671-5p sensitized breast cancer cells to cisplatin, 5-fluorouracil (5-FU) and epirubicin exposure. Host cell reactivation (HCR) assays showed that miR-671-5p reduces DNA repair capability in post-drug exposed breast cancer cells. cDNA microarray data revealed that differentially expressed genes when miR-671-5p was transfected are associated with cell proliferation, invasion, cell cycle, and EMT. These data indicate that miR-671-5p functions as a tumor suppressor miRNA in breast cancer by directly targeting FOXM1. Hence, miR-671-5p may serve as a novel therapeutic target for breast cancer management.
authors.affiliation: Department of Medicine (Division of Genomic Medicine), The George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Tan
authors.affiliation: Department of Medicine (Division of Genomic Medicine), The George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
authors.forename: Yebo
authors.initials: Y
authors.lastname: Fu
authors.affiliation: Department of Medicine (Division of Genomic Medicine), The George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
authors.forename: Liang
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Medicine (Division of Genomic Medicine), The George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
authors.forename: Woojin
authors.initials: W
authors.lastname: Lee
authors.affiliation: Department of Statistics, The George Washington University, Washington, DC, USA.
authors.forename: Yinglei
authors.initials: Y
authors.lastname: Lai
authors.affiliation: Department of Pathology, The George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
authors.forename: Katayoon
authors.initials: K
authors.lastname: Rezaei
authors.affiliation: Department of Pathology, The George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
authors.forename: Sana
authors.initials: S
authors.lastname: Tabbara
authors.affiliation: Department of Pathology, The George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
authors.forename: Patricia
authors.initials: P
authors.lastname: Latham
authors.affiliation: Department of Surgery, The George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
authors.forename: Christine B
authors.initials: CB
authors.lastname: Teal
authors.affiliation: Research Lab and International Collaboration, Bon Secours Cancer Institute, Bon Secours Health System, Richmond, VA, USA.
authors.forename: Yan-Gao
authors.initials: YG
authors.lastname: Man
authors.affiliation: Department of Medicine (Division of Hematology/Oncology), The George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Siegel
authors.affiliation: Department of Radiology, The George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
authors.forename: Rachel F
authors.initials: RF
authors.lastname: Brem
authors.affiliation: Department of Medicine (Division of Genomic Medicine), The George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
authors.forename: Sidney W
authors.initials: SW
authors.lastname: Fu
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D002945:Cisplatin / Q000494:pharmacology; D015536:Down-Regulation; D015251:Epirubicin / Q000494:pharmacology; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005472:Fluorouracil / Q000494:pharmacology; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors / Q000235:genetics* / Q000378:metabolism; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D061986:MCF-7 Cells; D035683:MicroRNAs / Q000235:genetics*; D018613:Microscopy, Confocal; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000970:Antineoplastic Agents; C107585:FOXM1 protein, human; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors; C568637:MIRN671 microRNA, human; D035683:MicroRNAs; D015251:Epirubicin; D002945:Cisplatin; D005472:Fluorouracil
keywords: EMT; FOXM1; breast cancer; miR-671-5p; tumor suppressor