title: BRCA mutations cause reduction in miR-200c expression in triple negative breast cancer.
abstract: Triple negative breast cancer (TNBC) is the most aggressive and poorly understood subclass of breast cancer (BC). Over the recent years, miRNA expression studies have been providing certain detailed overview that aberrant expression of miRNAs is associated with TNBC. Although TNBC tumors are strongly connected with loss of function of BRCA genes, there is no knowledge about the effect of BRCA mutation status on miRNA expressions in TNBC cases. The aims of this study were to evaluate the expression profile of miRNAs that plays role in TNBC progression and the role of BRCA mutations in their regulation. The expression level of BC associated 13 miRNAs was analyzed in 7 BRCA mutations positive, 6 BRCA mutations negative TNBC cases and 20 non-tumoral tissues using RT-PCR. According to RT2 Profiler PCR Array Data Analysis, let-7a expression was 4.67 fold reduced in TNBCs as compared to normal tissues (P=0.031). In addition, miR-200c expression was 5.75 fold reduced in BRCA mutation positive TNBC tumors (P=0.005). Analysis revealed a negative correlation between miR-200c and VEGFA expressions (r=-468). Thus, miR-200c may be involved in invasion and metastasis in TNBC cases with BRCA mutation. In this study we provide the knowledge on the first report of association between microRNA-200c and BRCA mutations in TNBC. Further studies and evaluations are required, but this miRNA may provide novel therapeutic molecular targets for TNBC treatment and new directions for the development of anticancer drugs.
authors.affiliation: Vocational School of Health Services, Uludag University, Bursa, Turkey.
authors.forename: Elif
authors.initials: E
authors.lastname: Erturk
authors.affiliation: Department of Medical Biology, Faculty of Medicine, Uludag University, Bursa, Turkey. Electronic address: gcecener@uludag.edu.tr.
authors.forename: Gulsah
authors.initials: G
authors.lastname: Cecener
authors.affiliation: Department of Medical Biology, Faculty of Medicine, Uludag University, Bursa, Turkey; Department of Medical Biology, Institute of Health Sciences, Uludag University, Bursa, Turkey.
authors.forename: Gulcin
authors.initials: G
authors.lastname: Tezcan
authors.affiliation: Department of Medical Biology, Faculty of Medicine, Uludag University, Bursa, Turkey.
authors.forename: Unal
authors.initials: U
authors.lastname: Egeli
authors.affiliation: Department of Medical Biology, Faculty of Medicine, Uludag University, Bursa, Turkey.
authors.forename: Berrin
authors.initials: B
authors.lastname: Tunca
authors.affiliation: Department of General Surgery, Faculty of Medicine, Uludag University, Bursa, Turkey.
authors.forename: Sehsuvar
authors.initials: S
authors.lastname: Gokgoz
authors.affiliation: Department of Pathology, Faculty of Medicine, Uludag University, Bursa, Turkey.
authors.forename: Sahsine
authors.initials: S
authors.lastname: Tolunay
authors.affiliation: Department of General Surgery, Faculty of Medicine, Uludag University, Bursa, Turkey.
authors.forename: Ismet
authors.initials: I
authors.lastname: Tasdelen
mesh_terms: D000328:Adult; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D064726:Triple Negative Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human; C533896:MIRN200 microRNA, human; D035683:MicroRNAs; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C487931:mirnlet7 microRNA, human
keywords: BRCA1/2 gene mutations; MicroRNA; Triple negative breast cancer; miR-200c