miR-214 modulates cisplatin sensitivity of osteosarcoma cells through regulation of anaerobic glycolysis
| Autor: | Song Yd, Jian Zheng, Li Dd, Guan Y, Wang Yl |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
musculoskeletal diseases
0301 basic medicine medicine.medical_specialty Antineoplastic Agents Bone Neoplasms Oxidative phosphorylation Biology 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation Internal medicine Cell Line Tumor medicine Humans Glycolysis miR-214 Osteosarcoma General Medicine medicine.disease Warburg effect Up-Regulation MicroRNAs 030104 developmental biology Endocrinology Anaerobic glycolysis Cell culture Drug Resistance Neoplasm 030220 oncology & carcinogenesis Cancer research Cisplatin |
| Zdroj: | Cellular and molecular biology (Noisy-le-Grand, France). 63(9) |
| ISSN: | 1165-158X |
| Popis: | Osteosarcoma is the most frequent primary bone tumor originating from adolescents and young adults. Despite improvements in the chemo- or radio- therapy of osteosarcoma patients, survival rate has not increased and drug resistance becomes a major factor that limits the effectiveness. Therefore, investigation of new treatment modalities is urgently required to optimize therapeutic options. Our previous study described an oncogenic role of miR-214 through promotion of osteosarcoma cells proliferation. In this study, we report miR-214 contributes to cisplatin resistance in osteosarcoma cells. Overexpression of miR-214 decreased the cisplatin sensitivity. By establishing an osteosarcoma cisplatin resistant cell line, we find miR-214 is significantly upregulated in cisplatin resistant cells. Moreover, we show miR-214 promotes anaerobic glycolysis rates of osteosarcoma cells but suppresses mitochondrial oxidative phosphorylation. Consistently, cisplatin resistant cells exhibit upregulated glycolysis but decreased mitochondrial oxidative phosphorylation, a phenotype called "Warburg effect”. Finally, we demonstrate inhibition of glycolysis by either glycolysis inhibitor or miR-214 inhibition significantly re-sensitizes cisplatin resistant osteosarcoma cells. In summary, this study illustrates a miRNA-involved chemosensitivity of osteosarcoma and will contribute to the developments of therapeutic agents for the anti-chemoresistance treatments. |
| Databáze: | OpenAIRE |
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