Downregulation of microRNA-26a is associated with metastatic potential and the poor prognosis of osteosarcoma patients

Song,Qi-Chun; Shi,Zhi-Bin; Zhang,Yong-Tao; Ji,Le; Wang,Kun‑Zheng; Duan,Da-Peng; Dang,Xiao-Qian

doi:10.3892/or.2014.2989

Downregulation of microRNA-26a is associated with metastatic potential and the poor prognosis of osteosarcoma patients

Authors:
- Qi-Chun Song
- Zhi-Bin Shi
- Yong-Tao Zhang
- Le Ji
- Kun‑Zheng Wang
- Da-Peng Duan
- Xiao-Qian Dang
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Affiliations: Department of Orthopedics, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China, Department of Orthopedics, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi 710068, P.R. China
Published online on: January 21, 2014 https://doi.org/10.3892/or.2014.2989
Pages: 1263-1270

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Abstract

Accumulating evidence indicates that microRNAs are involved in multiple processes in cancer development and progression. microRNA-26a (miR-26a) has been identified as a tumor suppressor and its downregulation is associated with poor prognosis in several types of human cancer. However, the specific function of miR-26a in osteosarcoma remains unclear. In the present study, we found that the expression of miR-26a in osteosarcoma tissues and cell lines was much lower than that in the normal controls, respectively. In addition, downregulation of miR-26a more frequently occurred in osteosarcoma specimens with adverse clinical stage and with the presence of distant metastasis. Moreover, multivariate survival analyses demonstrated that loss of miR-26a is an independent prognostic factor for both disease-free and overall survival in osteosarcoma. In addition, restoration of miR-26a expression inhibited the invasion and migration in osteosarcoma cells, and miR-26a directly inhibited enhancer of zeste homolog 2 (EZH2) expression by targeting its 3'-UTR. Moreover, EZH2 was upregulated and inversely correlated with miR-26a expression in the osteosarcoma tissues. Thus, for the first time, we provide convincing evidence that downregulation of miR-26a is associated with tumor aggressiveness and tumor metastasis, and miR-26a inhibits cell migration and invasion by targeting the EZH2 gene in osteosarcoma. Thus, miR-26a is an independent prognostic marker for osteosarcoma patients.

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