Overexpression of miR-506 suppresses proliferation and promotes apoptosis of osteosarcoma cells by targeting astrocyte elevated gene-1

Yao,Jie; Qin,Li; Miao,Sen; Wang,Xiangshan; Wu,Xuejian

doi:10.3892/ol.2016.4827

Overexpression of miR-506 suppresses proliferation and promotes apoptosis of osteosarcoma cells by targeting astrocyte elevated gene-1

Authors:
- Jie Yao
- Li Qin
- Sen Miao
- Xiangshan Wang
- Xuejian Wu
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Affiliations: Orthopedics Department, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China, Orthopedics Department 3,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
Published online on: July 8, 2016 https://doi.org/10.3892/ol.2016.4827
Pages: 1840-1848
Copyright: © Yao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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 cells in vitro and inhibited tumor formation in 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 osteosarcoma in 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 apoptosis in 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.

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