Dataset Information

MiR-29b-1-5p is altered in BRCA1 mutant tumours and is a biomarker in basal-like breast cancer.

ABSTRACT: Depletion of BRCA1 protein in mouse mammary glands results in defects in lactational development and increased susceptibility to mammary cancer. Extensive work has focussed on the role of BRCA1 in the normal breast and in the development of breast cancer, the cell of origin for BRCA1 tumours and the protein-coding genes altered in BRCA1 deficient cells. However, the role of non-coding RNAs in BRCA1-deficient cells is poorly understood. To evaluate miRNA expression in BRCA1 deficient mammary cells, RNA sequencing was performed on the mammary glands of Brca1 knockout mice. We identified 140 differentially expressed miRNAs, 9 of which were also differentially expressed in human BRCA1 breast tumours or familial non-BRCA1 patients and during normal gland development. We show that BRCA1 binds to putative cis-elements in promoter regions of the miRNAs with the potential to regulate their expression, and that four miRNAs (miR-29b-1-5p, miR-664, miR-16-2 and miR-744) significantly stratified the overall survival of basal-like tumours. Importantly the prognostic value of miR-29b-1-5p was higher in significance than several commonly used clinical biomarkers. These results emphasise the role of Brca1 in modulating expression of miRNAs and highlights the potential for BRCA1 regulated miRNAs to be informative biomarkers associated with BRCA1 loss and survival in breast cancer.

SUBMITTER: Milevskiy MJG

PROVIDER: S-EPMC6173367 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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MiR-29b-1-5p is altered in BRCA1 mutant tumours and is a biomarker in basal-like breast cancer.

Milevskiy Michael J G MJG Sandhu Gurveen K GK Wronski Anna A Korbie Darren D Brewster Brooke L BL Shewan Annette A Edwards Stacey L SL French Juliet D JD Brown Melissa A MA

Oncotarget 20180911 71

Depletion of BRCA1 protein in mouse mammary glands results in defects in lactational development and increased susceptibility to mammary cancer. Extensive work has focussed on the role of BRCA1 in the normal breast and in the development of breast cancer, the cell of origin for BRCA1 tumours and the protein-coding genes altered in BRCA1 deficient cells. However, the role of non-coding RNAs in BRCA1-deficient cells is poorly understood. To evaluate miRNA expression in BRCA1 deficient mammary cell ...[more]

PMID: 30323900

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Project description:PurposeBreast cancer (BC) is characterized by concealed onset, delayed diagnosis, and high fatality rates making it particularly dangerous to patients' health. The purpose of this study was to use comprehensive bioinformatics analysis and experimental verification to find a new biomarker for BC diagnosis.MethodsWe comprehensively analyzed microRNA (miRNA) and mRNA expression profiles from the Gene Expression Omnibus (GEO) and screened out differentially-expressed (DE) miRNAs and mRNAs. We used the miRNet website to predict potential DE-miRNA target genes. Using the Database for Annotation, Visualization and Integrated Discovery (DAVID), we performed Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses on overlapping potential target genes and DE-mRNAs. The protein-protein interaction (PPI) network was then established. The miRNA-mRNA regulatory network was constructed using Cytoscape and the analysis results were visualized. We verified the expression of the most up-regulated DE-miRNA using reverse transcription and a quantitative polymerase chain reaction in BC tissue. The diagnostic value of the most up-regulated DE-miRNA was further explored across three levels: plasma-derived exosomes, cells, and cell exosomes.ResultsOur comprehensive bioinformatics analysis and experimental results showed that hsa-miR-21-5p was significantly up-regulated in BC tissue, cells, and exosomes. Our results also revealed that tumor-derived hsa-miR-21-5p could be packaged in exosomes and released into peripheral blood. Additionally, when evaluating the diagnostic value of plasma exosomal hsa-miR-21-5p, we found that it was significantly up-regulated in BC patients. Receiver operating characteristic (ROC) analysis also confirmed that hsa-miR-21-5p could effectively distinguish healthy people from BC patients. The sensitivity and specificity were 86.7% and 93.3%, respectively.ConclusionThis study's results showed that plasma exosomal hsa-miR-21-5p could be used as a biomarker for BC diagnosis.

Dataset Information

MiR-29b-1-5p is altered in BRCA1 mutant tumours and is a biomarker in basal-like breast cancer.

Publications

MiR-29b-1-5p is altered in BRCA1 mutant tumours and is a biomarker in basal-like breast cancer.

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