MicroRNA-221 promotes cisplatin resistance in osteosarcoma cells by targeting PPP2R2A. Issue 7 (10th July 2019)

• Record Type: Journal Article
• Authors: Yu, Wen-chao; Chen, Hui-hao; Qu, Yan-yan; Xu, Chun-wei; Yang, Chen; Liu, Yan
• Is Part Of: Bioscience reports. Volume 39:Issue 7(2019)
• Publication Date: 2019-07-10
• Subjects: cisplatin -- microRNA-221 -- osteosarcoma cells -- PPP2R2A; Molecular biology -- Periodicals; Cytology -- Periodicals; 572.8
• DOI: 10.1042/BSR20190198
• Languages: English
• ISSNs: 0144-8463

Abstract

Abstract : 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.