Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Pichler, M; Ress, AL; Winter, E; Stiegelbauer, V; Karbiener, M; Schwarzenbacher, D; Scheideler, M; Ivan, C; Jahn, SW; Kiesslich, T; Gerger, A; Bauernhofer, T; Calin, GA; Hoefler, G.
MiR-200a regulates epithelial to mesenchymal transition-related gene expression and determines prognosis in colorectal cancer patients.
Br J Cancer. 2014; 110(6):1614-1621
Doi: 10.1038/bjc.2014.51
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- Führende Autor*innen der Med Uni Graz
- Pichler Martin
- Co-Autor*innen der Med Uni Graz
- Bauernhofer Thomas
- Gerger Armin
- Höfler Gerald
- Jahn Stephan
- Karbiener Michael
- Lembeck Anna Lena
- Ninaus Daniela
- Stiegelbauer Verena
- Winter Elke
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- Abstract:
- MicroRNAs (miRNAs) regulate the biological properties of colorectal cancer (CRC) cells and might serve as potential prognostic factors and therapeutic targets. In this study, we therefore globally profiled miRNAs associated with E-cadherin expression in CRC cells in an attempt to identify miRNAs that are associated with aggressive clinical course in CRC patients. Two CRC cell lines (Caco-2 and HRT-18) with different E-cadherin expression pattern were profiled for differences in abundance for more than 1000 human miRNAs using microarray technology. One of the most differentially expressed miRNAs, miR-200a was evaluated for its prognostic role in a cohort of 111 patients and independently validated in 217 patients of the Cancer Genome Atlas data set. To further characterise the biological role of miR-200a expression in CRC, in vitro miR-200a inhibition and overexpression were performed and the effects on cellular growth, apoptosis and epithelial-mesenchymal transition (EMT)-related gene expression were explored. In situ hybridisation specifically localised miR-200a in CRC cells. In both cohorts, a low miR-200a expression was associated with poor survival (P<0.05). Multivariate Cox regression analysis identified low levels of miR-200a expression as an independent prognostic factor with respect to cancer-specific survival (HR=2.04, CI=1.28-3.25, P<0.002). Gain and loss of function assays for miR-200a in vitro led to a significantly differential and converse expression of EMT-related genes (P<0.001.) A low expression of miR-200a was also observed in cancer stem cell-enriched spheroid growth conditions (P<0.05). In conclusion, our data suggest that low miR-200a expression is associated with poor prognosis in CRC patients. MiR-200a has a regulatory effect on EMT and is associated with cancer stem cell properties in CRC.
- Find related publications in this database (using NLM MeSH Indexing)
- Aged -
- Apoptosis - genetics
- Caco-2 Cells -
- Cell Growth Processes - genetics
- Colorectal Neoplasms - genetics Colorectal Neoplasms - pathology
- Epithelial-Mesenchymal Transition - genetics
- Female -
- Gene Expression -
- Humans -
- In Situ Hybridization -
- Kaplan-Meier Estimate -
- Male -
- MicroRNAs - genetics
- Middle Aged -
- Multivariate Analysis -
- Oligonucleotide Array Sequence Analysis -
- Prognosis -
- Retrospective Studies -
- Transfection -
- Find related publications in this database (Keywords)
- colorectal cancer
- non-coding RNA
- microRNA
- prognosis