miR-142 acts as a tumor suppressor in osteosarcoma cell lines by targeting Rac1

Zheng,Zhonghui; Ding,Muliang; Ni,Jiangdong; Song,Deye; Huang,Jun; Wang,Junjie

doi:10.3892/or.2014.3687

miR-142 acts as a tumor suppressor in osteosarcoma cell lines by targeting Rac1

Authors:
- Zhonghui Zheng
- Muliang Ding
- Jiangdong Ni
- Deye Song
- Jun Huang
- Junjie Wang
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Affiliations: Department of Orthopaedics, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, P.R. China
Published online on: December 22, 2014 https://doi.org/10.3892/or.2014.3687
Pages: 1291-1299

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Abstract

Although the 5-year survival rate of osteosarcoma (OS) has risen to ~60-70%, a substantial portion of patients still respond poorly to chemotherapy and have a high risk of relapse or metastasis even after curative resection. In this study, we found that the expression of miR-142 was significantly reduced in OS tissues and OS cell lines, while Ras-related C3 botulinum toxin substrate 1 (Rac1) expression was increased in the OS tissues and OS cell lines compared with expression in the controls. We then demonstrated that miR-142 regulated Rac1 expression at the transcriptional and translational levels by directly targeting its 3'-untranslated region (3'UTR). In addition, by loss- and gain-of function experiments, we investigated the role of miR-142 in OS cell lines and found that miR-142 acted as a tumor suppressor in the OS cell lines and inhibited cell proliferation and cell invasion and arrested cell cycle in the S phase. Furthermore, miR-142 inhibited osteosarcoma cell invasion by inducing E-cadherin expression and reducing expression of matrix metalloproteinase 2 (MMP2) and MMP9. Thus, overexpression of miR-142 and/or knockdown of Rac1 would be a novel target for OS therapy in the future.

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