Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
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SHR Neuro Krebs Kardio Lipid Stoffw Microb
Behringer, A; Stoimenovski, D; Porsch, M; Hoffmann, K; Behre, G; Grosse, I; Kalinski, T; Haybaeck, J; Nass, N.
Relationship of micro-RNA, mRNA and eIF Expression in Tamoxifen-Adapted MCF-7 Breast Cancer Cells: Impact of miR-1972 on Gene Expression, Proliferation and Migration.
Biomolecules. 2022; 12(7):
Doi: 10.3390/biom12070916
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Web of Science
PubMed
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- Co-Autor*innen der Med Uni Graz
- Haybäck Johannes
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- Abstract:
- BACKGROUND: Tamoxifen-adapted MCF-7-Tam cells represent an in-vitro model for acquired tamoxifen resistance, which is still a problem in clinics. We here investigated the correlation of microRNA-, mRNA- and eukaryotic initiation factors (eIFs) expression in this model. METHODS: MicroRNA- and gene expression were analyzed by nCounter and qRT-PCR technology; eIFs by Western blotting. Protein translation mode was determined using a reporter gene assay. Cells were transfected with a miR-1972-mimic. RESULTS: miR-181b-5p,-3p and miR-455-5p were up-, miR-375, and miR-1972 down-regulated and are significant in survival analysis. About 5% of the predicted target genes were significantly altered. Pathway enrichment analysis suggested a contribution of the FoxO1 pathway. The ratio of polio-IRES driven to cap-dependent protein translation shifted towards cap-dependent initiation. Protein expression of eIF2A, -4G, -4H and -6 decreased, whereas eIF3H was higher in MCF-7-Tam. Significant correlations between tamoxifen-regulated miRNAs and eIFs were found in representative breast cancer cell lines. Transfection with a miR-1972-mimic reverses tamoxifen-induced expression for a subset of genes and increased proliferation in MCF-7, but reduced proliferation in MCF-7-Tam, especially in the presence of 4OH-tamoxifen. Migration was inhibited in MCF-7-Tam cells. Translation mode remained unaffected. CONCLUSIONS: miR-1972 contributes to the orchestration of gene-expression and physiological consequences of tamoxifen adaption.
- Find related publications in this database (using NLM MeSH Indexing)
- Antineoplastic Agents, Hormonal - pharmacology, therapeutic use
- Breast Neoplasms - drug therapy, genetics, metabolism
- Cell Line, Tumor - administration & dosage
- Cell Movement - administration & dosage
- Cell Proliferation - administration & dosage
- Drug Resistance, Neoplasm - administration & dosage
- Female - administration & dosage
- Gene Expression - administration & dosage
- Gene Expression Regulation, Neoplastic - administration & dosage
- Humans - administration & dosage
- MCF-7 Cells - administration & dosage
- MicroRNAs - metabolism
- RNA, Messenger - genetics
- Tamoxifen - pharmacology, therapeutic use
- Find related publications in this database (Keywords)
- breast cancer
- tamoxifen
- MCF-7
- gene expression
- eukaryotic initiation factors