MicroRNA-603 functions as an oncogene by suppressing BRCC2 protein translation in osteosarcoma

Ma,Chengbin; Zhan,Chuan; Yuan,Hongmou; Cui,Yan; Zhang,Zhiyu

doi:10.3892/or.2016.4718

MicroRNA-603 functions as an oncogene by suppressing BRCC2 protein translation in osteosarcoma

Authors:
- Chengbin Ma
- Chuan Zhan
- Hongmou Yuan
- Yan Cui
- Zhiyu Zhang
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Affiliations: Department of Spinal Surgery, Department of Orthopedics, The Fourth Affiliated Hospital of China Medical University, Huanggu District, Shenyang 110032, P.R. China, Department of Traumatology Surgery, Department of Orthopedics, The Fourth Affiliated Hospital of China Medical University, Huanggu District, Shenyang 110032, P.R. China, Department of Joint Surgery, Department of Orthopedics, The Fourth Affiliated Hospital of China Medical University, Huanggu District, Shenyang 110032, P.R. China, Department of Joint Surgery and Surgical Oncology, Department of Orthopedics, The Fourth Affiliated Hospital of China Medical University, Huanggu District, Shenyang 110032, P.R. China
Published online on: March 30, 2016 https://doi.org/10.3892/or.2016.4718
Pages: 3257-3264

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Abstract

The present study was conducted to investigate the expression of miR-603 in osteosarcoma cells, and the effect of miR-603 on the biological behavior and expression of breast cancer cell 2 (BRCC2) in osteosarcoma cells. In the present study, qRT-PCR was used to measure the levels of miRNA and mRNA. The results showed that miR-603 was significantly upregulated in human osteosarcoma tissues and cell lines. MTT and colony formation assays were employed to evaluate the role of miR-603 in the regulation of osteosarcoma cell proliferation. The results showed that overexpression of miR-603 promoted the proliferation of MG-63 and U2OS cells. Furthermore, a nude mouse subcutaneous tumor model indicated that miR-603 promoted osteosarcoma growth in vivo. Moreover, miR-603 expression levels were increased in patients with distant metastasis in comparison with levels in patients without distant metastasis. We discovered that BRCC2 may be a target of miR-603. Our results demonstrated that overexpression of miR-603 suppressed BRCC2 protein expression, and an miR-603 inhibitor enhanced BRCC2 protein expression as determined by western blot assay and immunohistochemical analysis. Luciferase reporter assays confirmed that BRCC2 is a direct target of miR-603 in osteosarcoma cells, and the results suggest that miR-603 downregulates BRCC2 expression in osteosarcoma via translational inhibition. Finally, we found that the reduction in BRCC2 expression induced by miR-603 was responsible for the enhanced colony formation and proliferative ability noted in the MG-63 and U2OS cells. In conclusion, miR-603 enhanced osteosarcoma growth by downregulation of BRCC2 expression via translational inhibition.

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