Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Rashed, MH; Kanlikilicer, P; Rodriguez-Aguayo, C; Pichler, M; Bayraktar, R; Bayraktar, E; Ivan, C; Filant, J; Silva, A; Aslan, B; Denizli, M; Mitra, R; Ozpolat, B; Calin, GA; Sood, AK; Abd-Ellah, MF; Helal, GK; Berestein, GL.
Exosomal miR-940 maintains SRC-mediated oncogenic activity in cancer cells: a possible role for exosomal disposal of tumor suppressor miRNAs.
Oncotarget. 2017; 8(12):20145-20164
Doi: 10.18632/oncotarget.15525
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PubMed
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- Co-Autor*innen der Med Uni Graz
- Pichler Martin
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- Abstract:
- Exosomes have emerged as important mediators of diverse biological functions including tumor suppression, tumor progression, invasion, immune escape and cell-to-cell communication, through the release of molecules such as mRNAs, miRNAs, and proteins. Here, we identified differentially expressed exosomal miRNAs between normal epithelial ovarian cell line and both resistant and sensitive ovarian cancer (OC) cell lines. We found miR-940 as abundant in exosomes from SKOV3-IP1, HeyA8, and HeyA8-MDR cells. The high expression of miR-940 is associated with better survival in patients with ovarian serous cystadenocarcinoma. Ectopic expression of miR-940 inhibited proliferation, colony formation, invasion, and migration and triggered G0/G1 cell cycle arrest and apoptosis in OC cells. Overexpression of miR-940 also inhibited tumor cell growth in vivo. We showed that proto-oncogene tyrosine-protein kinase (SRC) is directly targeted by miR-940 and that miR-940 inhibited SRC expression at mRNA and protein levels. Following this inhibition, the expression of proteins downstream of SRC, such as FAK, paxillin and Akt was also reduced. Collectively, our results suggest that OC cells secrete the tumor-suppressive miR-940 into the extracellular environment via exosomes, to maintain their invasiveness and tumorigenic phenotype.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Apoptosis -
- Biomarkers, Tumor - genetics
- Biomarkers, Tumor - metabolism
- Cell Proliferation -
- Exosomes - genetics
- Female -
- Gene Expression Regulation, Neoplastic -
- Genes, Tumor Suppressor -
- Humans -
- Mice -
- Mice, Nude -
- MicroRNAs - genetics
- Ovarian Neoplasms - genetics
- Ovarian Neoplasms - metabolism
- Ovarian Neoplasms - pathology
- Signal Transduction -
- Tumor Cells, Cultured -
- Xenograft Model Antitumor Assays -
- src-Family Kinases - genetics
- src-Family Kinases - metabolism
- Find related publications in this database (Keywords)
- exosomes
- ovarian cancer
- miR-940
- SRC
- tumor suppressive