Silencing of lncRNA HOXA11-AS inhibits cell migration, invasion, proliferation, and promotes apoptosis in human glioma cells via upregulating microRNA-125a: in vitro and in vivo studies

Abstract

Glioma is an aggressive nervous system tumor with poor prognosis. Although the therapeutic strategies to overcome glioma have been improved largely recent years, the potential mechanism of its carcinogenesis remains largely unclear. The present study aimed to investigate the role of long non-coding RNA HOMEOBOX A11 antisense RNA (lncRNA HOXA11-AS) in glioma, and further to explore the underlying mechanism. We forst detected the level of lncRNA HOXA11-AS and microRNA-125a (miR-125a) in glioma tissues and human glioma U251 cells using quantitative real time polymerase chain reaction (qRT-PCR). Then, effect of lncRNA HOXA11-AS silencing on U251 cell migration, invasion, proliferation, and apoptosis was determined. Meanwhile, the expression of caspase-3/8/9 and several tumor-related genes was measured by Western blotting and qRT-PCR. Dual luciferase activity assay was used to confirm the targeting relationship between lncRNA HOXA11-AS and miR-125a. Results indicated that lncRNA HOXA11-AS was significantly increased in U251 cells and positively correlated with glioma World Health Organization (WHO) grade in glioma tissues. lncRNA HOXA11-AS silencing could inhibit cell migration, invasion, proliferation, and promote apoptosis, while up-regulate the expression of caspase-3/8/9 and Bax, inhibit the expression of Bcl-2 and gab2 in U251 cells. miR-125a inhibitor could partially reverse these effects of lncRNA HOXA11-AS silencing on U251 cells. In vivo assays also indicated that lncRNA HOXA11-AS inhibitor could inhibit glioma growth in vivo by regulating the expression of miR-125a. In conclusion, we revealed that lncRNA HOXA11-AS acted as an oncogene in glioma via interacting with miR-125a and considered that lncRNA HOXA11-AS was a potential therapeutic target for glioma.