Long non-coding RNA MEG3 inhibits cell growth of gliomas by targeting miR-93 and inactivating PI3K/AKT pathway.

Gliomas are the most common cancers in the brain, accompanied with high morbility, occurrence, disability and mortality. Long non-coding RNAs (lncRNAs) have been proposed as promoter or inhibitor in many cancer processes. Previous findings have indicated that lncRNA-maternally expressed gene 3 (MEG3) is involved in tumorigenesis of several cancers, including glioma. However, the underlying mechanism of MEG3 in glioma remains elusive. In our study, MEG3 was found downregulated in glioma tissues compared with normal brain tissues. Downregulated expression of MEG3 was also detected in two human glioma cell lines (U-251, M059J) compared with normal astrocyte cells. MEG3 was then overexpressed by ligating to a lentiviral vector. Overexpressed MEG3 inhibited the proliferation of U-251 cells, and restrained the expression of proliferation marker proteins Ki67 and proliferating cell nuclear antigen (PCNA). However, cell apoptosis rate of U-251 cells and the expression of apoptosis marker proteins (caspase-3 and caspase-9) were elevated by MEG3. Furthermore, miR-93 was predicted a direct target of lncRNA-MEG3 by bioinformatics analysis. Overexpressed MEG3 counteracted the role of miR-93 in facilitating proliferation and inhibiting apoptosis in U-251 cells. Moreover, MEG3 restained the activation of phosphatidylinositol 3 kinase/protein kinase B (PI3K/AKT) pathway by reducing cytomembrane translocation of AKT. Finally, the in vivo experiment revealed that MEG3 strongly reduced tumor growth, tumor volume and the expression of Ki67 and PCNA. lncRNA-MEG3 also inhibited the level of miR-93 and the expression of PI3K/AKT pathway related proteins in vivo. Taken together, our research indicated a MEG3-miR-93-PI3K-AKT pathway in regulating the growth of glioma, providing a promising therapy for glioma.