TGF-β1-induced miR-202 mediates drug resistance by inhibiting apoptosis in human osteosarcoma

• DOI: 10.1007/s00432-015-2028-9
• Publication Date: 2015-08-14T09:14:30Z
• Authors: Zaijun Lin; Dianwen Song; Haifeng Wei; Xinghai Yang; Tielong Liu; Wangjun Yan; Jianru Xiao
• Keywords: 0301 basic medicine; Osteosarcoma; Osteoblasts; Reverse Transcriptase Polymerase Chain Reaction; Blotting, Western; RNA-Binding Proteins; Apoptosis; Bone Neoplasms; Real-Time Polymerase Chain Reaction; 3. Good health; Gene Expression Regulation, Neoplastic; Transforming Growth Factor beta1; MicroRNAs; 03 medical and health sciences; Drug Resistance, Neoplasm; Tumor Cells, Cultured; Humans; RNA, Messenger; RNA, Small Interfering; Apoptosis Regulatory Proteins; Cell Proliferation; Signal Transduction

A number of studies have demonstrated that microRNAs play a critical role in osteosarcoma progression, therapy and drug resistance. MicroRNA-202 has proven to be dysregulated in many human cancer studies. This study aimed to explore miR-202 contributions to drug resistance in osteosarcoma.miR-202 expression was measured by real-time PCR in patient tissues, cell lines or cells treated with TGF-β1, using siRNA to knock down the expression of Smad2, Smad3 and Smad4. miR-202 mimics, inhibitor and scramble siRNA were transfected into osteosarcoma cells to observe effects on cell apoptosis and drug resistance. Moreover, relationships of miR-202 level with PDCD4 were investigated by luciferase reporter assay, real-time PCR and Western blotting.We found that miR-202 is overexpressed in osteosarcoma tissues when compared with normal human osteoblasts and TGF-β1 can induce the expression of miR-202. Transfection of miR-202 mimics into osteosarcoma cell lines significantly promotes chemotherapy resistance by targeting PDCD4, a tumor suppressor which is involved in apoptosis. In contrast, transfection of miR-202 inhibitor enhances the drug sensitivity and apoptosis.This study provides new insights into miRNA-202 in osteosarcoma as a potential molecular target for chemotherapy.