title: Claudin 1 Expression Levels Affect miRNA Dynamics in Human Basal-Like Breast Cancer Cells.
abstract: Deemed a putative tumor suppressor in breast cancer, the tight junction protein claudin 1 has now been shown to be highly expressed in the basal-like molecular subtype. Moreover, recent in vitro studies show that claudin 1 can regulate breast cancer cell motility and proliferation. Herein, we investigated whether microRNA (miRNA) dysregulation is associated with alterations in the level of claudin 1. Using next-generation sequencing (NGS), we identified seven miRNAs (miR-9-5p, miR-9-3p, let-7c, miR-127-3p, miR-99a-5p, miR-129-5p, and miR-146a-5p) that were deregulated as a consequence of claudin 1 overexpression in the MDA-MB231 human breast cancer (HBC) cell line. Most of these miRNAs have been associated with tumor suppression in a variety of cancers, including breast cancer. Moreover, through gene expression profiling analysis, we identified epithelial-mesenchymal transition-related genes, including platelet-derived growth factor receptor-beta (PDGFRB) and cadherin 1 (CDH1, E cadherin), whose downregulation correlated with claudin 1 overexpression. Collectively, we show for the first time that in HBC, claudin 1 can alter the dynamics of a number of miRNAs involved in tumor progression. Our data suggest that the dysregulated expression of these miRNAs, in conjunction with the high claudin 1 levels, could serve as a useful biomarker that identifies a subset of tumors within the poorly characterized basal-like subtype of breast cancer. Further studies are warranted to determine the role of these miRNAs in facilitating the function of claudin 1 in breast cancer.
authors.affiliation: 1 Department of Medical Microbiology and Infectious Diseases, Faculty of Health Sciences, College of Medicine, University of Manitoba , Winnipeg, Manitoba, Canada .|2 Molecular PathoBiology, National Microbiology Laboratory, Canadian Science Centre for Human and Animal Health, Public Health Agency of Canada , Winnipeg, Manitoba, Canada .
authors.forename: Anna
authors.initials: A
authors.lastname: Majer
authors.affiliation: 3 Department of Pathology, University of Manitoba , Winnipeg, Manitoba, Canada .|4 Department of Physiology and Pathophysiology, University of Manitoba , Winnipeg, Manitoba, Canada .
authors.forename: Anne A
authors.initials: AA
authors.lastname: Blanchard
authors.affiliation: 2 Molecular PathoBiology, National Microbiology Laboratory, Canadian Science Centre for Human and Animal Health, Public Health Agency of Canada , Winnipeg, Manitoba, Canada .
authors.forename: Sarah
authors.initials: S
authors.lastname: Medina
authors.affiliation: 1 Department of Medical Microbiology and Infectious Diseases, Faculty of Health Sciences, College of Medicine, University of Manitoba , Winnipeg, Manitoba, Canada .|2 Molecular PathoBiology, National Microbiology Laboratory, Canadian Science Centre for Human and Animal Health, Public Health Agency of Canada , Winnipeg, Manitoba, Canada .
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Booth
authors.affiliation: 3 Department of Pathology, University of Manitoba , Winnipeg, Manitoba, Canada .|4 Department of Physiology and Pathophysiology, University of Manitoba , Winnipeg, Manitoba, Canada .
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Myal
mesh_terms: D001943:Breast Neoplasms / Q000175:diagnosis / Q000235:genetics*; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D062445:Claudin-1 / Q000235:genetics* / Q000378:metabolism*; D015536:Down-Regulation / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics; D018295:Neoplasms, Basal Cell / Q000235:genetics*
chemical_list: D015820:Cadherins; D062445:Claudin-1; D035683:MicroRNAs