MiR-127 and miR-376a act as tumor suppressors by in vivo targeting of COA1 and PDIA6 in giant cell tumor of bone
| Autor: | Burkhard Lehner, Ingrid Herr, Jörg Fellenberg, Libo Yin, Heiner Sähr, Georg W. Omlor, Zhefu Zhao |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Cancer Research Stromal cell Protein Disulfide-Isomerases Bone Neoplasms Chick Embryo Biology Transfection Malignant transformation Electron Transport Complex IV 03 medical and health sciences 0302 clinical medicine Cell Line Tumor medicine Animals Humans Gene silencing Genes Tumor Suppressor Giant Cell Tumors Cell Proliferation Giant Cell Tumor of Bone medicine.disease Transplantation MicroRNAs Chorioallantoic membrane 030104 developmental biology Oncology Giant cell 030220 oncology & carcinogenesis Immunology Cancer research Heterografts Giant-cell tumor of bone |
| Zdroj: | Cancer Letters. 409:49-55 |
| ISSN: | 0304-3835 |
| DOI: | 10.1016/j.canlet.2017.08.029 |
| Popis: | Giant cell tumors of bone (GCTB) are generally benign bone tumors associated with expansive osteolytic defects, a high rate of recurrence and potential malignant transformation. We recently observed silencing of miR-127-3p and miR-376a-3p in GCTB and identified COA1 and PDIA6 as their target genes. Here, we investigate the impact of these microRNAs and their target genes on tumor engraftment and progression of giant cell tumor stromal cells (GCTSC) in vivo by xenotransplantation on the chorioallantoic membrane of chicken eggs. Prior to transplantation, the neoplastic GCTSCs were transfected with miRNA mimics or siRNAs directed against their target genes. Restoration of miR-127-3p and miR-376a-3p reduced the tumor take rate to 17% and 47% compared to 95% in the controls. The tumor volumes were significantly reduced to 29% by both miRNAs. Silencing of COA1 and PDIA6 significantly decreased the tumor volumes to 37.7% and 42.7%, while the tumor take rates remained stable. Our results indicate that re-expression of miR-127-3p and miR-376a-3p induces a strong tumor suppressor effect in GCTSC, which is partially mediated via COA1 and PDIA6 . |
| Databáze: | OpenAIRE |
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