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Induction of Mesenchymal-Epithelial Transitions in Sarcoma Cells
Published on: April 7, 2017
MicroRNA-128 inhibits EMT of human osteosarcoma cells by directly targeting integrin α2
Xinsheng Liu1, Zhiyong Liang1, Kehai Gao1
1Department of Orthopaedics, Yidu Central Hospital of Weifang, Qingzhou, 262500, Shandong, People's Republic of China.
Abstract:
Deregulated expression of miRNAs contributes to the development of osteosarcoma. The present study was to evaluate the level of miR-128 and integrin α2 (ITGA2) in osteosarcoma tissues and cells. We further investigated the molecular mechanisms of miR-128 and ITGA2 in osteosarcoma cell lines. In the present study, we found that miR-128 expression was down-regulated in osteosarcoma tissues and MG-63, U2OS, and SAOS-2 cells (all p < 0.001). By contrast, ITGA2 was up-regulated. Furthermore, we found that miR-128 overexpression suppressed cell migration and invasion of MG-63 cells. Mechanically, miR-128 overexpression inhibited epithelial-mesenchymal transition (EMT) of MG-63 cells. Importantly, we identified that the 3'-untranslated region (3'-UTR) of ITGA2 was a direct target of miR-128. Luciferase reporter assays confirmed that miR-128 binding to the 3'-UTR regions of ITGA2 inhibited the expression of ITGA2 in MG-63 cells. At the same time, overexpressed ITGA2 also reversed EMT inhibited by miR-128. In conclusion, this study suggested that high miR-128 expression suppressed osteosarcoma cell migration, invasion, and EMT development through targeting ITGA2, which may be recommended as a therapeutic target for osteosarcoma.
Insights
MicroRNA 128 (miR-128) is down-regulated in osteosarcoma, suppressing tumor cell migration and invasion. Targeting integrin α2 (ITGA2) with miR-128 offers a potential therapeutic strategy for osteosarcoma.
Area of Science:
- Oncology
- Molecular Biology
- Gene Regulation
Background:
- Aberrant microRNA (miRNA) expression is implicated in osteosarcoma development.
- The specific roles of miR-128 and integrin α2 (ITGA2) in osteosarcoma remain incompletely understood.
Purpose of the Study:
- To investigate the expression levels of miR-128 and ITGA2 in osteosarcoma.
- To elucidate the molecular mechanisms underlying the interaction between miR-128 and ITGA2 in osteosarcoma cells.
Main Methods:
- Quantitative real-time PCR to assess miR-128 and ITGA2 expression.
- Cell migration and invasion assays using osteosarcoma cell lines (MG-63, U2OS, SAOS-2).
- Luciferase reporter assays to confirm direct targeting of ITGA2 by miR-128.
Main Results:
- miR-128 expression was significantly downregulated, while ITGA2 was upregulated in osteosarcoma tissues and cells.
- Overexpression of miR-128 inhibited cell migration, invasion, and epithelial-mesenchymal transition (EMT) in MG-63 cells.
- miR-128 directly targeted the 3'-untranslated region (3'-UTR) of ITGA2, suppressing its expression. Overexpressed ITGA2 reversed the inhibitory effects of miR-128 on EMT.
Conclusions:
- The miR-128/ITGA2 axis plays a critical role in osteosarcoma progression.
- Restoring miR-128 expression suppresses osteosarcoma cell migration, invasion, and EMT by targeting ITGA2.
- ITGA2 represents a potential therapeutic target for osteosarcoma treatment.
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