Overexpression of miR-506 suppresses proliferation and promotes apoptosis of osteosarcoma cells by targeting astrocyte elevated gene-1.
There is increasing evidence that microRNAs (miRs) are implicated in tumor development and progression; however, their specific roles in osteosarcoma are not well understood. The aim of the present study was to investigate the role of miR-506 in the pathogenesis of osteosarcoma. The expression levels of miR-506 and astrocyte elevated gene-1 (AEG-1) mRNA were detected using quantitative polymerase chain reaction, and the protein levels of AEG-1, β-catenin, c-myc and cyclin D1 were determined using western blot analysis. The effects of miR-506 and AEG-1 on cell viability, colony forming ability and apoptosis were assessed using MTT assay, colony formation assay, and flow cytometry, respectively. Lucifer reporter assays were used to demonstrate whether AEG-1 is a direct target of miR-506. The present study identified that miR-506 was downregulated in osteosarcoma tissues and cells. Overexpression of miR-506 suppressed the proliferation and induced apoptosis in osteosarcoma cellsin vitroand inhibited tumor formationin vivo. Overexpression of miR-506 significantly inhibited the luciferase activity of AEG-1 with a wild-type 3'-untranslated region, providing clear evidence that AEG-1 was a direct and functional downstream target of miR-506. Similar to the overexpression of miR-506, downregulation of AEG-1 lead to an inhibitory effect on osteosarcomain vitro. Furthermore, overexpression of miR-506 or downregulation of AEG-1 inhibited the Wnt/β-catenin signaling pathway, and inhibition of this pathway by β-catenin small interfering RNA or CGP049090, a small molecule inhibitor, suppressed cell proliferation and induced apoptosisin vitro. Overall, the present data indicated that miR-506 functions as a tumor suppressor by targeting AEG-1 in osteosarcoma via the regulation of the Wnt/β-catenin signaling pathway.
Orthopedics Department, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China; Spine Department 3, Zhengzhou Orthopedics Hospital, Zhengzhou, Henan 450052, P.R. China.
Jie
J
Yao
Orthopedics Department 3,The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
Li
L
Qin
Spine Department 3, Zhengzhou Orthopedics Hospital, Zhengzhou, Henan 450052, P.R. China.
Sen
S
Miao
Spine Department 3, Zhengzhou Orthopedics Hospital, Zhengzhou, Henan 450052, P.R. China.
Xiangshan
X
Wang
Orthopedics Department 3,The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
Xuejian
X
Wu
Wnt/β-catenin pathway; astrocyte elevated gene-1; miR-506; osteosarcoma