Long Non-coding RNA XIST Promotes Glioma Tumorigenicity and Angiogenesis by Acting as a Molecular Sponge of miR-429.

Abstract

Glioma is a worldwide malignancy, which displays significantly active metastasis and angiogenesis. Interaction between long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) has been shown to play crucial role in regulating tumor properties. However, the potential of lncRNA X-inactive specific transcript (XIST) to function as a miRNA regulator and its relevance in glioma tumorigenicity and angiogenesis have so far remained unclear. Expression analysis of lncRNA XIST in glioma cells revealed its significant up-regulation. Interestingly, silencing of XIST repressed both metastatic and pro-angiogenic ability in vitro as well as in vivo. Subsequent studies revealed that lncRNA XIST expression inversely correlated with miR-429 expression in glioma cells; miR-429 modulated XIST expression by directly targeting the XIST gene sequence. In addition, miR-429 inhibitor restored metastatic and pro-angiogenic ability of gliomas abolished by silencing XIST. Our data provide insight into the key roles of the lncRNA-miRNA functional network in gliomas, which can aid in developing new therapeutic strategies for gliomas through clinical trials.