MiR-221/222 promote human glioma cell invasion and angiogenesis by targeting TIMP2.
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.
State Key Laboratory of Cancer Biology, Department of Immunology, Fourth Military Medical University, Xi'an, 710032, China.
Fan
F
Yang
Wei
W
Wang
Chunhui
C
Zhou
Wenjin
W
Xi
Lu
L
Yuan
Xu
X
Chen
Yufang
Y
Li
Angang
A
Yang
Jianning
J
Zhang
Tao
T
Wang
D017209:Apoptosis / Q000235:genetics; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000235:genetics* / Q000473:pathology; D006801:Humans; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D009361:Neoplasm Invasiveness / Q000235:genetics; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic / Q000235:genetics; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000096:biosynthesis* / Q000235:genetics
D035683:MicroRNAs; D019716:Tissue Inhibitor of Metalloproteinase-2; C525709:MIR221, human; C525710:MIR222, human; C560823:TIMP2 protein, human