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| Description
| - MiR-34a acts as a candidate tumour suppressor gene, and its expression is reduced in several cancer types. We aimed to study miR-34a expression in breast cancer and its correlation with tumour characteristics and clinical outcome, and regulatory links with other genes. We analysed miR-34a expression in 1,172 breast tumours on TMAs. 25% of the tumours showed high, 43% medium and 32% low expression of miR-34a. High miR-34a expression associated with poor prognostic factors for breast cancer: positive nodal status (p = 0.006), high tumour grade (p { 0.0001), ER-negativity (p = 0.0002), HER2-positivity (p = 0.0002), high proliferation rate (p { 0.0001), p53-positivity (p { 0.0001), high cyclin E (p { 0.0001) and gamma H2AX (p { 0.0001). However, multivariate analysis adjusting for conventional prognostic factors indicated that high miR-34a expression in fact associated with a lower risk of recurrence or death from breast cancer (HR = 0.63, 95% CI = 0.41-0.96, p = 0.031). Gene expression analysis by differential miR-34a expression revealed an expression signature with an effect on both the 5-year and 10-year survival of the patients (p { 0.001). Functional genomic analysis highlighted a novel regulatory role of the transcription factor MAZ, apart from the known control by p53, on the expression of miR-34a and a number of miR-34a targets. Our findings suggest that while miR-34a expression activation is a marker of aggressive breast tumour phenotype it exerts an independent effect for a lower risk of recurrence or death from breast cancer. We also present an expression signature of 190 genes associated with miR-34a expression. Our analysis for regulatory loops suggest that MAZ and p53 transcription factors co-operate in modulating miR-34a, as well as miR-34a targets involved in several cellular pathways.
- MiR-34a acts as a candidate tumour suppressor gene, and its expression is reduced in several cancer types. We aimed to study miR-34a expression in breast cancer and its correlation with tumour characteristics and clinical outcome, and regulatory links with other genes. We analysed miR-34a expression in 1,172 breast tumours on TMAs. 25% of the tumours showed high, 43% medium and 32% low expression of miR-34a. High miR-34a expression associated with poor prognostic factors for breast cancer: positive nodal status (p = 0.006), high tumour grade (p { 0.0001), ER-negativity (p = 0.0002), HER2-positivity (p = 0.0002), high proliferation rate (p { 0.0001), p53-positivity (p { 0.0001), high cyclin E (p { 0.0001) and gamma H2AX (p { 0.0001). However, multivariate analysis adjusting for conventional prognostic factors indicated that high miR-34a expression in fact associated with a lower risk of recurrence or death from breast cancer (HR = 0.63, 95% CI = 0.41-0.96, p = 0.031). Gene expression analysis by differential miR-34a expression revealed an expression signature with an effect on both the 5-year and 10-year survival of the patients (p { 0.001). Functional genomic analysis highlighted a novel regulatory role of the transcription factor MAZ, apart from the known control by p53, on the expression of miR-34a and a number of miR-34a targets. Our findings suggest that while miR-34a expression activation is a marker of aggressive breast tumour phenotype it exerts an independent effect for a lower risk of recurrence or death from breast cancer. We also present an expression signature of 190 genes associated with miR-34a expression. Our analysis for regulatory loops suggest that MAZ and p53 transcription factors co-operate in modulating miR-34a, as well as miR-34a targets involved in several cellular pathways. (en)
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| Title
| - MiR-34a Expression Has an Effect for Lower Risk of Metastasis and Associates with Expression Patterns Predicting Clinical Outcome in Breast Cancer
- MiR-34a Expression Has an Effect for Lower Risk of Metastasis and Associates with Expression Patterns Predicting Clinical Outcome in Breast Cancer (en)
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| skos:prefLabel
| - MiR-34a Expression Has an Effect for Lower Risk of Metastasis and Associates with Expression Patterns Predicting Clinical Outcome in Breast Cancer
- MiR-34a Expression Has an Effect for Lower Risk of Metastasis and Associates with Expression Patterns Predicting Clinical Outcome in Breast Cancer (en)
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| skos:notation
| - RIV/61989592:15110/11:10225465!RIV15-MSM-15110___
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| http://linked.open...avai/riv/aktivita
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| http://linked.open...avai/riv/aktivity
| - P(ED0030/01/01), Z(MSM6198959216)
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| http://linked.open...iv/cisloPeriodika
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| http://linked.open...vai/riv/dodaniDat
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| http://linked.open...aciTvurceVysledku
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| http://linked.open.../riv/druhVysledku
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| http://linked.open...iv/duvernostUdaju
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| http://linked.open...titaPredkladatele
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| http://linked.open...dnocenehoVysledku
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| http://linked.open...ai/riv/idVysledku
| - RIV/61989592:15110/11:10225465
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| http://linked.open...riv/jazykVysledku
| |
| http://linked.open.../riv/klicovaSlova
| - MICROARRAY; BIOINFORMATICS; FAMILY; TARGET; CELLS; APOPTOSIS; MICRORNAS; GENE-EXPRESSION; DOWN-REGULATION; DNA-DAMAGE RESPONSE (en)
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| http://linked.open.../riv/klicoveSlovo
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| http://linked.open...odStatuVydavatele
| - US - Spojené státy americké
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| http://linked.open...ontrolniKodProRIV
| |
| http://linked.open...i/riv/nazevZdroje
| |
| http://linked.open...in/vavai/riv/obor
| |
| http://linked.open...ichTvurcuVysledku
| |
| http://linked.open...cetTvurcuVysledku
| |
| http://linked.open...vavai/riv/projekt
| |
| http://linked.open...UplatneniVysledku
| |
| http://linked.open...v/svazekPeriodika
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| http://linked.open...iv/tvurceVysledku
| - Bártek, Jiří
- Aittomaki, Kristiina
- Blomqvist, Carl
- Butzow, Ralf
- Greco, Dario
- Heikkila, Paivi
- Heikkinen, Tuomas
- Jamshidi, Maral
- Kaur, Sippy
- Nevanlinna, Heli
- Peurala, Hanna
- Bartková, Jiřina
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| http://linked.open...n/vavai/riv/zamer
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| issn
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| number of pages
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| http://localhost/t...ganizacniJednotka
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