MiR-221/222 promote human glioma cell invasion and angiogenesis by targeting TIMP2
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miR-221/222 are two highly homologous microRNAs that are frequently upregulated in solid tumors. However, the effects of miR-221/222 in malignant gliomas have not been investigated thoroughly. In this study, we found that miR-221/222 were significantly upregulated in human glioma samples and glioma cell lines. Both gain- and loss-of-function studies showed that miR-221/222 regulate cell proliferation, the cell cycle and apoptosis, in addition to, invasion, metastasis, and angiogenesis in glioma cell lines. Subsequent investigations revealed that TIMP2 is a direct target of miR-221/222, and overexpression of TIMP2 reduced the miR-221/222-mediated invasion, metastasis, and angiogenesis of glioma cells. Taken together, our results suggest that the suppression of miR-221/222 may be a feasible approach for inhibiting the malignant behaviors of glioma.
KeywordsmiR-221/222 TIMP2 Gliomas Invasion and metastasis Angiogenesis
Vascular endothelial growth factor
Tissue inhibitors of metalloproteinases
Human umbilical vein endothelial cells
This work was supported by the National Natural Sciences Foundation of China (81172289 and 81472633).
Conflicts of interest
- 11.Guo M, Jiang Z, Zhang X, Lu D, Ha AD, Sun J, Du W, Wu Z, Hu L, Khadarian K, Shen J, Lin Z. miR-656 inhibits glioma tumorigenesis through repression of BMPR1A. Carcinogenesis. 2014Google Scholar
- 30.Lu Y, Roy S, Nuovo G, Ramaswamy B, Miller T, Shapiro C, et al. Anti-microRNA-222 (anti-miR-222) and -181B suppress growth of tamoxifen-resistant xenografts in mouse by targeting TIMP3 protein and modulating mitogenic signal. J Biol Chem. 2011;286(49):42292–302.CrossRefPubMedPubMedCentralGoogle Scholar