CircNT5E Acts as a Sponge of miR-422a to Promote Glioblastoma Tumorigenesis

Circular RNA and long noncoding RNA function as efficient miRNA sponges that regulate gene expression in eukaryotes. However, the sponges of functional miRNAs in glioblastoma remain largely unknown. Here, we identify a subset of circRNAs and lncRNAs that are specifically increased in miR-422a-downregulated glioblastoma tissues. We characterized a novel circRNA derived from NT5E, named circNT5E, that is regulated by ADARB2 binding to sites flanking circRNA-forming introns. We hypothesized that circNT5E may serve as a sponge against miR-422a in glioblastoma tumorigenesis. circNT5E controlled multiple pathologic processes, including cell proliferation, migration, and invasion. circNT5E directly bound miR-422a and inhibited miR-422a activity. Furthermore, circNT5E was observed to sponge other miRNAs, exhibiting tumor suppressor-like features in glioblastoma. Taken together, these findings highlight a novel oncogenic function of circRNA in glioblastoma tumorigenesis.<b>Significance:</b> Microarray profiling of circRNA/lncRNA/mRNA in glioblastoma identifies circNT5E as an oncogenic circular RNA and a sponge of miR-422a. <i>Cancer Res; 78(17); 4812-25. ©2018 AACR</i>.