BRCA mutations cause reduction in miR-200c expression in triple negative breast cancer

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 strongl...

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Veröffentlicht in:Gene 2015-02, Vol.556 (2), p.163-169
Hauptverfasser: Erturk, Elif, Cecener, Gulsah, Tezcan, Gulcin, Egeli, Unal, Tunca, Berrin, Gokgoz, Sehsuvar, Tolunay, Sahsine, Tasdelen, Ismet
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container_end_page 169
container_issue 2
container_start_page 163
container_title Gene
container_volume 556
creator Erturk, Elif
Cecener, Gulsah
Tezcan, Gulcin
Egeli, Unal
Tunca, Berrin
Gokgoz, Sehsuvar
Tolunay, Sahsine
Tasdelen, Ismet
description 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. •We evaluated the expression profile of miRNAs that plays role in TNBC progression.•We examined the role of BRCA mutations in regulation of miRNAs in TNBC.•miR-200c may be involved in invasion and metastasis in BRCA mutated TNBC cases.
doi_str_mv 10.1016/j.gene.2014.11.047
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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. •We evaluated the expression profile of miRNAs that plays role in TNBC progression.•We examined the role of BRCA mutations in regulation of miRNAs in TNBC.•miR-200c may be involved in invasion and metastasis in BRCA mutated TNBC cases.</description><identifier>ISSN: 0378-1119</identifier><identifier>EISSN: 1879-0038</identifier><identifier>DOI: 10.1016/j.gene.2014.11.047</identifier><identifier>PMID: 25445393</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Adult ; BRCA1 Protein - genetics ; BRCA1/2 gene mutations ; BRCA2 Protein - genetics ; Disease Progression ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; MicroRNA ; MicroRNAs - genetics ; Middle Aged ; miR-200c ; Mutation ; Triple negative breast cancer ; Triple Negative Breast Neoplasms - genetics ; Triple Negative Breast Neoplasms - pathology ; Vascular Endothelial Growth Factor A - genetics</subject><ispartof>Gene, 2015-02, Vol.556 (2), p.163-169</ispartof><rights>2014</rights><rights>Copyright © 2014. 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subjects Adult
BRCA1 Protein - genetics
BRCA1/2 gene mutations
BRCA2 Protein - genetics
Disease Progression
Female
Gene Expression Regulation, Neoplastic
Humans
MicroRNA
MicroRNAs - genetics
Middle Aged
miR-200c
Mutation
Triple negative breast cancer
Triple Negative Breast Neoplasms - genetics
Triple Negative Breast Neoplasms - pathology
Vascular Endothelial Growth Factor A - genetics
title BRCA mutations cause reduction in miR-200c expression in triple negative breast cancer
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