miR-221/222 promote malignant progression of glioma through activation of the Akt pathway.
MicroRNAs (miRNAs) are short regulatory RNAs that negatively modulate protein expression at a post-transcriptional level. Emerging evidence suggests that miRNAs play important roles in the pathogenesis of several types of cancers. However, the further mechanisms of miRNA remain unknown. In this study, we aimed to explore the coordinated function of miR-221/222 in glioma by bioinformatics and experiment methods. Bioinformatics analysis revealed that miR-221/222 had the potential to regulate about 70 common target genes and may exert a cooperative effect on regulation and function via Akt signaling pathway. Overexpression of miR-221/222 increased glioma cell proliferation and invasion in vitro and induced glioma growth in a subcutaneous mouse model. Furthermore, miR-221/222 overexpression resulted in an obvious activation of p-Akt and significant changes of Akt-related gene expression in glioma cells. Our results suggest that miR-221/222 co-enhance the glioma malignant phenotype via activation of the Akt pathway mediated by regulation of common gene expression.
Zhang
Junxia
J
Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, P.R. China.
Han
Lei
L
Ge
Youlin
Y
Zhou
Xuan
X
Zhang
Anling
A
Zhang
Chunzhi
C
Zhong
Yue
Y
You
Yongping
Y
Pu
Peiyu
P
Kang
Chunsheng
C
D000818:Animals; D001932:Brain Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019295:Computational Biology; D030541:Databases, Genetic; D004789:Enzyme Activation; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D005838:Genotype; D005910:Glioma / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D010641:Phenotype; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction / Q000235:genetics; D013997:Time Factors; D014161:Transduction, Genetic; D047368:Tumor Burden
D035683:MicroRNAs; D051057:Proto-Oncogene Proteins c-akt; C525709:MIR221, human; C525710:MIR222, human