miR-92a promotes tumor growth of osteosarcoma by targeting PTEN/AKT signaling pathway

Xiao,Jie; Yu,Weifeng; Hu,Kongzu; Li,Maoqiang; Chen,Jianwei; Li,Zhanchun

doi:10.3892/or.2017.5484

miR-92a promotes tumor growth of osteosarcoma by targeting PTEN/AKT signaling pathway

Authors:
- Jie Xiao
- Weifeng Yu
- Kongzu Hu
- Maoqiang Li
- Jianwei Chen
- Zhanchun Li
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Affiliations: Department of Anesthesiology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200127, P.R. China, Department of Orthopaedic Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China, Department of Orthopaedic Surgery, Hangzhou First People's Hospital, Hangzhou, Zhejiang 310006, P.R. China, Department of Orthopaedic Surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200127, P.R. China
Published online on: March 2, 2017 https://doi.org/10.3892/or.2017.5484
Pages: 2513-2521

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Abstract

MicroRNAs (miRNAs) play critical roles in human cancers including osteosarcoma (OS). miR-92a has been found to be a cancer-related miRNA in many cancer types and it is upregulated in OS cell lines. However, the expression and biological function of miR-92a in OS have not been investigated. In this study, we showed that miR-92a expression was increased in OS tissues, and its high expression was correlated with clinical stage, T classification and histological differentiation. Furthermore, patients with high expression of miR-92a had a significantly poorer survival rate. Functionally, miR-92a overexpression promoted the proliferation and cell cycle progression, and inhibited apoptosis in MG-63 cells. While inhibition of miR-92a showed contrary effects with reduced proliferation, cell cycle arrest at G1 phase and increased apoptosis in U2OS cells. Moreover, we confirmed that miR-92a inhibition reversed the tumor growth of OS cells in nude mice. Phosphatase and tensin homolog (PTEN), a well-known tumor suppressor, was confirmed to be the direct downstream target of miR-92a in OS. Notably, miR-92a consequently regulated the expression of the downstream targets of PTEN/AKT signaling pathway including p-Akt(Ser473), mTOR, p-p27(Thr157) and p-MDM2(Ser166). Furthermore, PTEN knockdown abrogated the functional effects of miR-92a silencing on the proliferation, apoptosis and cell cycle progression in OS cells. Thus, miR-92a that exerts an oncogenic role by targeting PTEN/AKT pathway in OS potentially acts as a biomarker and drug-target.

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