title: Expression status of let-7a and miR-335 among breast tumors in patients with and without germ-line BRCA mutations.
abstract: The genetic factors of cancer predisposition remain elusive in the majority of familial and/or early-onset cases of breast cancer (BC). This type of BC is promoted by germ-line mutations that inactivate BRCA1 or BRCA2. On the other hand, recent studies have indicated that alterations in the levels of miRNA expression are linked to this disease. Although BRCA1 and BRCA2 gene mutations have been reported to commonly lead to alterations in genes that encode cancer-related proteins, little is known regarding the putative impact of these mutations on noncoding miRNAs. In the present study, we aimed to determine whether miRNA dysregulation is involved in the pathogenesis of BRCA-mutated BC. An expression analysis of 14 human miRNAs previously shown to be related to BC diagnosis, prognosis, and drug resistance was conducted using tissues from 60 familial and/or early-onset patients whose peripheral blood samples had been screened for BRCA1 and BRCA2 mutations through sequence analysis. Let-7a and miR-335 expression levels were significantly downregulated in the tumors of patients with a BRCA mutation compared with those of patients without a BRCA mutation (P = 0.04 and P = 0.02, respectively). Our results defined the associations between the expression status of let-7a and miR-335 and BRCA mutations. The expression analysis of these miRNAs might be used as biomarkers of the BRCA mutation status of early-onset and/or familial BC.
authors.affiliation: Department of Medical Biology, Institute of Health Sciences, Uludag University, Bursa, Turkey.
authors.forename: Elif
authors.initials: E
authors.lastname: Erturk
authors.forename: Gulsah
authors.initials: G
authors.lastname: Cecener
authors.forename: Unal
authors.initials: U
authors.lastname: Egeli
authors.forename: Berrin
authors.initials: B
authors.lastname: Tunca
authors.forename: Gulcin
authors.initials: G
authors.lastname: Tezcan
authors.forename: Sehsuvar
authors.initials: S
authors.lastname: Gokgoz
authors.forename: Sahsine
authors.initials: S
authors.lastname: Tolunay
authors.forename: Ismet
authors.initials: I
authors.lastname: Tasdelen
mesh_terms: D000328:Adult; D000368:Aged; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D018095:Germ-Line Mutation; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D011379:Prognosis; D055815:Young Adult
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human; C556347:MIRN335 microRNA, human; D035683:MicroRNAs; C487931:mirnlet7 microRNA, human