MicroRNA-221 promotes cisplatin resistance in osteosarcoma cells by targeting PPP2R2A
| Autor: | Hui-hao Chen, Wen-chao Yu, Yan-yan Qu, Chen Yang, Chun-wei Xu, Yan Liu |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male medicine.medical_treatment Apoptosis Biochemistry PPP2R2A 0302 clinical medicine Cell Movement Gene expression Protein Phosphatase 2 Research Articles Osteosarcoma Chemistry microRNA-221 Osteoblast Transfection Prognosis Gene Expression Regulation Neoplastic medicine.anatomical_structure 030220 oncology & carcinogenesis Female medicine.drug Research Article Adult Adolescent Biophysics 03 medical and health sciences Young Adult Cell Line Tumor microRNA medicine Humans Neoplasm Invasiveness Molecular Biology Cell Proliferation Cisplatin Chemotherapy Osteoblasts Cell Biology osteosarcoma cells medicine.disease MicroRNAs 030104 developmental biology Cell culture Drug Resistance Neoplasm Cancer research |
| Zdroj: | Bioscience Reports |
| ISSN: | 1573-4935 |
| Popis: | Osteosarcoma (OS), the most common malignant bone tumor, is the main cause of cancer-related deaths in children and young adults. Despite the combination of surgery and multi-agent chemotherapy, patients with OS who develop resistance to chemotherapy or experience recurrence have a dismal prognosis. MicroRNAs (miRNAs) are a class of small noncoding RNAs that repress their targets by binding to the 3′-UTR and/or coding sequences, leading to the inhibition of gene expression. miR-221 is found to be up-regulated in tumors when compared with their matched normal osteoblast tissues. We also observed significant miR-221 up-regulation in the OS cell lines, MG-63, SaoS-2, and U2OS, when compared with the normal osteoblast cell line, HOb. Overexpression of miR-221 promoted OS cell invasion, migration, proliferation, and cisplatin resistance. MG-63 and SaoS-2 cells transfected with miR-221 mimics were more resistant to cisplatin. The IC50 of MG-63 cells transfected with control mimics was 1.24 μM. However, the IC50 of MG-63 cells overexpressing miR-221 increased to 7.65 μM. Similar results were found in SaoS-2 cells, where the IC50 for cisplatin increased from 3.65 to 8.73 μM. Thus, we report that miR-221 directly targets PP2A subunit B (PPP2R2A) in OS by binding to the 3′-UTR of the PPP2R2A mRNA. Restoration of PPP2R2A in miR-221-overexpressing OS cells recovers the cisplatin sensitivity of OS cells. Therefore, the present study suggests a new therapeutic approach by inhibiting miR-221 for anti-chemoresistance in OS. |
| Databáze: | OpenAIRE |
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