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miRNA expression patterns in normal breast tissue and invasive breast cancers of BRCA1 and BRCA2 germ-line mutation carriers.
- Source :
-
Oncotarget [Oncotarget] 2015 Oct 13; Vol. 6 (31), pp. 32115-37. - Publication Year :
- 2015
-
Abstract
- miRNA deregulation has been found to promote carcinogenesis. Little is known about miRNA deregulation in hereditary breast tumors as no miRNA expression profiling studies have been performed in normal breast tissue of BRCA1 and BRCA2 mutation carriers. miRNA profiles of 17 BRCA1- and 9 BRCA2-associated breast carcinomas were analyzed using microarrays. Normal breast tissues from BRCA1 and BRCA2 mutation carriers (both n = 5) and non-mutation carriers (n = 10) were also included. Candidate miRNAs were validated by qRT-PCR. Breast carcinomas showed extensive miRNA alteration compared to normal breast tissues in BRCA1 and BRCA2 mutation carriers. Moreover, normal breast tissue from BRCA1 mutation carriers already showed miRNA alterations compared to non-mutation carriers. Chromosomal distribution analysis showed several hotspots containing down- or up-regulated miRNAs. Pathway analysis yielded many similarities between the BRCA1 and BRCA2 axes with miRNAs involved in cell cycle regulation, proliferation and apoptosis. Lesser known pathways were also affected, including cellular movement and protein trafficking. This study provides a comprehensive insight into the potential role of miRNA deregulation in BRCA1/2-associated breast carcinogenesis. The observed extensive miRNA deregulation is likely the result of genome-wide effects of chromosomal instability caused by impaired BRCA1 or BRCA2 function. This study's results also suggest the existence of common pathways driving breast carcinogenesis in both BRCA1 and BRCA2 germ-line mutation carriers.
- Subjects :
- Adult
Aged
Aged, 80 and over
Biomarkers, Tumor genetics
Breast Neoplasms metabolism
Breast Neoplasms pathology
Carcinoma, Ductal, Breast genetics
Carcinoma, Ductal, Breast metabolism
Carcinoma, Ductal, Breast pathology
Carcinoma, Lobular genetics
Carcinoma, Lobular metabolism
Carcinoma, Lobular pathology
Carcinoma, Medullary genetics
Carcinoma, Medullary metabolism
Carcinoma, Medullary pathology
Case-Control Studies
Chromosomes, Human genetics
Female
Follow-Up Studies
Genetic Predisposition to Disease
Humans
Immunoenzyme Techniques
Microarray Analysis
Middle Aged
Neoplasm Grading
Neoplasm Invasiveness
Prognosis
RNA, Messenger genetics
Real-Time Polymerase Chain Reaction
Receptor, ErbB-2 metabolism
Receptors, Estrogen metabolism
Receptors, Progesterone metabolism
Reverse Transcriptase Polymerase Chain Reaction
Young Adult
BRCA1 Protein genetics
BRCA2 Protein genetics
Breast Neoplasms genetics
Germ-Line Mutation genetics
MicroRNAs genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1949-2553
- Volume :
- 6
- Issue :
- 31
- Database :
- MEDLINE
- Journal :
- Oncotarget
- Publication Type :
- Academic Journal
- Accession number :
- 26378051
- Full Text :
- https://doi.org/10.18632/oncotarget.5617