Long noncoding RNA lncARSR confers resistance to Adriamycin and promotes osteosarcoma progression
| Autor: | Peng Shen, Yanfeng Cheng |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Cancer Research
Immunology Apoptosis Rhodamine 123 Article Cellular and Molecular Neuroscience chemistry.chemical_compound Downregulation and upregulation Cell Line Tumor medicine Bone cancer Humans lcsh:QH573-671 Protein kinase B Cell Proliferation Cisplatin Osteosarcoma Chemistry lcsh:Cytology Correction Cell Biology Translational research medicine.disease Multiple drug resistance Doxorubicin Drug Resistance Neoplasm Cancer research Matrix Metalloproteinase 2 RNA Long Noncoding Signal transduction Signal Transduction medicine.drug |
| Zdroj: | Cell Death & Disease Cell Death and Disease, Vol 11, Iss 5, Pp 1-12 (2020) |
| ISSN: | 2041-4889 |
| Popis: | One of the significant challenges for chemotherapy is the appearance of resistance to compounds. Although several signaling pathways have been implicated in the development of Adriamycin (ADM) resistance, mechanisms involved in ADM-resistant osteosarcoma progression remain unknown. The present study attempted to illustrate the role of long noncoding RNA ARSR (lncARSR) in the development of adapted ADM resistance. We found lncARSR overexpressed in the Adriamycin-resistant cell lines U2OS/ADM and MG63/ADM, accompanied with acquired multidrug resistance against to paclitaxel and cisplatin. Overexpression of lncARSR triggered rhodamine 123 efflux and survival, as well as the migration of Adriamycin-resistant cells. Inversely, the depletion of lncARSR promoted rhodamine 123 retention and apoptosis, while reducing the motility of ADM-resistant cells. Further investigation revealed that the upregulation of lncARSR enhanced multidrug resistance-associated protein-1 (MRP1), apoptosis inhibitor Survivin, and matrix metalloproteinase-2 (MMP2) through activating AKT. The reduction of lncARSR overcame the resistance to ADM in U2OS/ADM mouse model. The current study gained novel evidence for understanding the mechanisms underlying adaptive ADM resistance and provided rationales to improve clinical outcomes of refractory osteosarcoma. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|