Malignant glioma is the most common and deadly
primary brain tumor in adults. However, the mechanisms underlying the
malignancy of
glioma remain unclear. In the present study, we found that
Fos-related antigen-2 (Fra-2) was overexpressed in most
glioma cells, and knockdown of Fra-2 prevented cell proliferation, migration, and invasion. Mechanistically, Fra-2 silencing led to a significant reduction in cell-cycle drivers (
Cyclin D1 and
Cyclin E1), one invasion-associated gene (MMP9), the mesenchymal marker (
Vimentin), and induction of the epithelial marker (
E-cadherin). Further study confirmed that miR-124-3p decreased the expression of Fra-2 via directly targeting the 3'-UTR, and transfection with miR-124-3p in
glioma cells inhibited expression of the above cell-cycle and EMT promoters. Phenotypic experiments also showed that overexpression of Fra-2 weakened the inhibitory effects of miR-124-3p on the proliferation, migration, and invasion of
glioma cells. In addition, Fra-2 knockdown impaired the malignant phenotypes enhanced by miR-124-3p inhibition, which suggested a crucial role for the miR-124-3p/Fra-2 pathway in
glioma development. Consistently, high expression of Fra-2 was closely associated with low miR-124-3p level and indicated a poor prognosis in patients with
glioma. In conclusion, this study indicates the existence of an aberrant miR-124-3p/Fra-2 pathway that results in
glioma aggressiveness, which suggests novel therapeutic opportunities for this fatal disease.