title: MicroRNA-603 functions as an oncogene by suppressing BRCC2 protein translation in osteosarcoma.
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.
authors.affiliation: Department of Spinal Surgery, Department of Orthopedics, The Fourth Affiliated Hospital of China Medical University, Huanggu District, Shenyang 110032, P.R. China.
authors.forename: Chengbin
authors.initials: C
authors.lastname: Ma
authors.affiliation: Department of Spinal Surgery, Department of Orthopedics, The Fourth Affiliated Hospital of China Medical University, Huanggu District, Shenyang 110032, P.R. China.
authors.forename: Chuan
authors.initials: C
authors.lastname: Zhan
authors.affiliation: Department of Traumatology Surgery, Department of Orthopedics, The Fourth Affiliated Hospital of China Medical University, Huanggu District, Shenyang 110032, P.R. China.
authors.forename: Hongmou
authors.initials: H
authors.lastname: Yuan
authors.affiliation: Department of Joint Surgery, Department of Orthopedics, The Fourth Affiliated Hospital of China Medical University, Huanggu District, Shenyang 110032, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Cui
authors.affiliation: 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.
authors.forename: Zhiyu
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001859:Bone Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D063646:Carcinogenesis / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D009368:Neoplasm Transplantation; D009857:Oncogenes; D012516:Osteosarcoma / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D014176:Protein Biosynthesis; D034622:RNA Interference; D016019:Survival Analysis
chemical_list: C000597759:MIRN603 microRNA, human; D035683:MicroRNAs