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MiR-221/222 promote human glioma cell invasion and angiogenesis by targeting TIMP2

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Tumor Biology

Abstract

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.

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Abbreviations

VEGF:

Vascular endothelial growth factor

TIMPs:

Tissue inhibitors of metalloproteinases

MMPs:

Metallopeptidases

ECM:

Extracellular matrix

HUVECs:

Human umbilical vein endothelial cells

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Acknowledgements

This work was supported by the National Natural Sciences Foundation of China (81172289 and 81472633).

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    Authors and Affiliations

    1. State Key Laboratory of Cancer Biology, Department of Immunology, Fourth Military Medical University, Xi’an, 710032, China

      Fan Yang, Wei Wang, Wenjin Xi, Xu Chen, Yufang Li, Angang Yang & Tao Wang

    2. Department of Neurosurgery, Navy General Hospital, Beijing, 100037, China

      Fan Yang, Chunhui Zhou & Jianning Zhang

    3. Department of Immunology and Pathogenic Biology, School of Medicine, Xi’an Jiaotong University, Xi’an, 710061, China

      Lu Yuan

    4. Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, Xi’an, 710032, China

      Fan Yang

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    1. Fan Yang
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    Correspondence to Jianning Zhang or Tao Wang.

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    Fan Yang and Wei Wang contributed equally to this work.

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    Yang, F., Wang, W., Zhou, C. et al. MiR-221/222 promote human glioma cell invasion and angiogenesis by targeting TIMP2. Tumor Biol. 36, 3763–3773 (2015). https://doi.org/10.1007/s13277-014-3017-3

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    • DOI: https://doi.org/10.1007/s13277-014-3017-3

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