Tumor Biology

, Volume 36, Issue 5, pp 3763–3773 | Cite as

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

  • Fan Yang
  • Wei Wang
  • Chunhui Zhou
  • Wenjin Xi
  • Lu Yuan
  • Xu Chen
  • Yufang Li
  • Angang Yang
  • Jianning Zhang
  • Tao Wang
Research Article


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.


miR-221/222 TIMP2 Gliomas Invasion and metastasis Angiogenesis 



Vascular endothelial growth factor


Tissue inhibitors of metalloproteinases




Extracellular matrix


Human umbilical vein endothelial cells



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

Conflicts of interest



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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Fan Yang
    • 1
    • 2
    • 4
  • Wei Wang
    • 1
  • Chunhui Zhou
    • 2
  • Wenjin Xi
    • 1
  • Lu Yuan
    • 3
  • Xu Chen
    • 1
  • Yufang Li
    • 1
  • Angang Yang
    • 1
  • Jianning Zhang
    • 2
  • Tao Wang
    • 1
  1. 1.State Key Laboratory of Cancer Biology, Department of ImmunologyFourth Military Medical UniversityXi’anChina
  2. 2.Department of NeurosurgeryNavy General HospitalBeijingChina
  3. 3.Department of Immunology and Pathogenic Biology, School of MedicineXi’an Jiaotong UniversityXi’anChina
  4. 4.Department of Neurosurgery, Xijing HospitalFourth Military Medical UniversityXi’anChina

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