Differential expression of the miR-17-92 cluster and miR-17 family in breast cancer according to tumor type; results from the Norwegian Women and Cancer (NOWAC) study
| Autor: | Eiliv Lund, Tonje Braaten, Khalid Al-Shibli, Lill-Tove Busund, Line Moi |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Oncology Microarray medicine.medical_treatment lcsh:Medicine MiRBase 0302 clinical medicine Breast cancer Cluster Analysis miR-17-92-cluster Principal Component Analysis Norway MicroRNA General Medicine Middle Aged VDP::Medical disciplines: 700::Basic medical dental and veterinary science disciplines: 710 Up-Regulation Gene Expression Regulation Neoplastic NOWAC Receptors Estrogen 030220 oncology & carcinogenesis Female RNA Long Noncoding Breast reduction miR-106b-25 cluster medicine.medical_specialty Down-Regulation Breast Neoplasms General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Internal medicine microRNA medicine Humans Tumor type Differential expression Aged business.industry Research Gene Expression Profiling lcsh:R Reproducibility of Results Cancer VDP::Medisinske Fag: 700::Basale medisinske odontologiske og veterinærmedisinske fag: 710 medicine.disease MicroRNAs 030104 developmental biology miR-17-family Case-Control Studies business |
| Zdroj: | Journal of Translational Medicine, Vol 17, Iss 1, Pp 1-20 (2019) Journal of Translational Medicine |
| Popis: | Background MicroRNAs (miRNAs) are promising biomarkers due to their structural stability and distinct expression profile in various cancers. We wanted to explore the miRNA expression in benign breast tissue and breast cancer subgroups in the Norwegian Women and Cancer study. Methods Specimens and histopathological data from study participants in Northern Norway diagnosed with breast cancer, and benign tissue from breast reduction surgery were collected. Main molecular subtypes were based on surrogate markers; luminal A (ER+ and/or PR+, HER2− and Ki67 ≤ 30%), luminal B (ER+ and/or PR+, HER2− and Ki67 > 30% or ER+ and/or PR+ and HER2+), HER2 positive (ER− and PR− and HER2+) and triple-negative (ER−, PR− and HER2−). RNA was extracted from formalin-fixed paraffin-embedded (FFPE) tissue, and miRNAs were successfully analyzed in 102 cancers and 36 benign controls using the 7th generation miRCURY LNA microarray containing probes targeting all human miRNAs as annotated in miRBASE version 19.0. Validation with RT-qPCR was performed. Results On average, 450 miRNAs were detected in each sample, and 304 miRNAs were significantly different between malignant and benign tissue. Subgroup analyses of cancer cases revealed 23 miRNAs significantly different between ER+ and ER− tumors, and 47 miRNAs different between tumors stratified according to grade. Significantly higher levels were found in high grade tumors for miR-17-5p (p = 0.006), miR-20a-5p (p = 0.007), miR-106b-5p (p = 0.007), miR-93-5p (p = 0.007) and miR-25-3p (p = 0.015) from the paralogous clusters miR-17-92 and miR-106b-25. Expression of miR-17-5p (p = 0.0029), miR-20a-5p (p = 0.0021), miR-92a-3p (p = 0.011) and miR-106b-5p (p = 0.021) was significantly higher in triple-negative tumors compared to the rest, and miR-17-5p and miR-20a-5p were significantly lower in luminal A tumors. Conclusions miRNA expression profiles were significantly different between malignant and benign tissue and between cancer subgroups according to ER− status, grade and molecular subtype. miRNAs in the miR-17-92 cluster and miR-17 family were overexpressed in high grade and triple-negative tumors associated with aggressive behavior. The expression and functional role of these miRNAs should be further studied in breast cancer to explore their potential as biomarkers in diagnostic pathology and clinical oncology. |
| Databáze: | OpenAIRE |
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