microRNA-194 suppresses osteosarcoma cell proliferation and metastasis in vitro and in vivo by targeting CDH2 and IGF1R

Han,Kang; Zhao,Tingbao; Chen,Xiang; Bian,Na; Yang,Tongtao; Ma,Qiong; Cai,Chengkui; Fan,Qingyu; Zhou,Yong; Ma,Baoan

doi:10.3892/ijo.2014.2571

microRNA-194 suppresses osteosarcoma cell proliferation and metastasis in vitro and in vivo by targeting CDH2 and IGF1R

Authors:
- Kang Han
- Tingbao Zhao
- Xiang Chen
- Na Bian
- Tongtao Yang
- Qiong Ma
- Chengkui Cai
- Qingyu Fan
- Yong Zhou
- Baoan Ma
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Affiliations: Department of Orthopedic Surgery, Orthopedics Oncology Institute of Chinese PLA, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, P.R. China, Department of Spinal Cord Injury, General Hospital of Jinan Military Area Command of Chinese PLA, Jinan, Shandong, P.R. China, Department of Baylor College of Medicine, Houston, TX, USA
Published online on: July 30, 2014 https://doi.org/10.3892/ijo.2014.2571
Pages: 1437-1449
Copyright: © Han et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

Studies have shown that miR-194 functions as a tumor suppressor and is associated with tumor growth and metastasis. We studied the effects of miR-194 in osteosarcoma and the possible mechanism by which miR-194 affected the survival, apoptosis and metastasis of osteosarcoma. Both human osteosarcoma cell lines SOSP-9607 and U2-OS were transfected with recombinant lentiviruses to regulate miR-194 expression. Overexpression of miR-194 partially inhibited the proliferation, migration, and invasion of osteosarcoma cells in vitro, as well as tumor growth and pulmonary metastasis of osteosarcoma cells in vivo. Potential miR-194 target genes were predicted using bioinformatics. Luciferase reporter assay, real-time quantitative PCR and western blotting confirmed that CDH2 (N-cadherin) and IGF1R were targets of miR-194. Using real-time quantitative PCR, we evaluated the expression of miR-194 and two miR-194 target genes, CDH2 and IGF1R in osteosarcoma samples from 107 patients and 99 formalin- or paraformalin-fixed paraffin-embedded tissues. The expressions of the target genes were also examined in osteosarcoma samples using immunohistochemistry. Overexpression of miR-194 inhibited tumor growth and metastasis of osteosarcoma probably by downregulating CDH2 and IGF1R. miR-194 may prove to be a promising therapeutic agent for osteosarcoma.

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