Medizinische Universität Graz - Research portal
Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Pehserl, AM; Ress, AL; Stanzer, S; Resel, M; Karbiener, M; Stadelmeyer, E; Stiegelbauer, V; Gerger, A; Mayr, C; Scheideler, M; Hutterer, GC; Bauernhofer, T; Kiesslich, T; Pichler, M.
Comprehensive Analysis of miRNome Alterations in Response to Sorafenib Treatment in Colorectal Cancer Cells.
Int J Mol Sci. 2016; 17(12):
Doi: 10.3390/ijms17122011
[OPEN ACCESS]
Web of Science
PubMed
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- Leading authors Med Uni Graz
- Pehserl Anna-Maria
- Pichler Martin
- Co-authors Med Uni Graz
- Bauernhofer Thomas
- Gerger Armin
- Hutterer Georg
- Karbiener Michael
- Lembeck Anna Lena
- Resel Margit
- Stadelmeyer Elke
- Stanzer Stefanie
- Stiegelbauer Verena
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- Abstract:
- MicroRNAs (miRNAs) are master regulators of drug resistance and have been previously proposed as potential biomarkers for the prediction of therapeutic response in colorectal cancer (CRC). Sorafenib, a multi-kinase inhibitor which has been approved for the treatment of liver, renal and thyroid cancer, is currently being studied as a monotherapy in selected molecular subtypes or in combination with other drugs in metastatic CRC. In this study, we explored sorafenib-induced cellular effects in Kirsten rat sarcoma viral oncogene homolog olog (KRAS) wild-type and KRAS-mutated CRC cell lines (Caco-2 and HRT-18), and finally profiled expression changes of specific miRNAs within the miRNome (>1000 human miRNAs) after exposure to sorafenib. Overall, sorafenib induced a time- and dose-dependent growth-inhibitory effect through S-phase cell cycle arrest in KRAS wild-type and KRAS-mutated CRC cells. In HRT-18 cells, two human miRNAs (hsa-miR-597 and hsa-miR-720) and two small RNAs (SNORD 13 and hsa-miR-3182) were identified as specifically sorafenib-induced. In Caco-2 cells, nine human miRNAs (hsa-miR-3142, hsa-miR-20a, hsa-miR-4301, hsa-miR-1290, hsa-miR-4286, hsa-miR-3182, hsa-miR-3142, hsa-miR-1246 and hsa-miR-720) were identified to be differentially regulated post sorafenib treatment. In conclusion, we confirmed sorafenib as a potential anti-neoplastic treatment strategy for CRC cells by demonstrating a growth-inhibitory and cell cycle-arresting effect of this drug. Changes in the miRNome indicate that some specific miRNAs might be relevant as indicators for sorafenib response, drug resistance and potential targets for combinatorial miRNA-based drug strategies.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Caco-2 Cells -
- Cell Cycle Checkpoints - drug effects
- Colorectal Neoplasms - drug therapy
- Colorectal Neoplasms - genetics
- Colorectal Neoplasms - pathology
- Drug Resistance, Neoplasm - genetics
- Gene Expression Regulation, Neoplastic -
- Humans -
- MicroRNAs - biosynthesis
- MicroRNAs - genetics
- Mutation -
- Niacinamide - administration & dosage
- Niacinamide - analogs & derivatives
- Phenylurea Compounds - administration & dosage
- Proto-Oncogene Proteins p21(ras) - genetics
- Sorafenib -
- Find related publications in this database (Keywords)
- colorectal cancer
- sorafenib
- miRNA