Zaijun Lin1, Dianwen Song1, Haifeng Wei1, Xinghai Yang1, Tielong Liu1, Wangjun Yan1, Jianru Xiao2. 1. Department of Bone Tumor Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, China. 2. Department of Bone Tumor Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, China. jianru365@163.com.
Abstract
PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: This study provides new insights into miRNA-202 in osteosarcoma as a potential molecular target for chemotherapy.
PURPOSE: 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 humancancer studies. This study aimed to explore miR-202 contributions to drug resistance in osteosarcoma. METHODS: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. RESULTS: 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. CONCLUSIONS: This study provides new insights into miRNA-202 in osteosarcoma as a potential molecular target for chemotherapy.
Entities:
Keywords:
Drug resistance; Osteosarcoma; PDCD4; miR-202
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