Regulation of a novel circATP8B4/miR-31-5p/nestin ceRNA crosstalk in proliferation, motility, invasion and radiosensitivity of human glioma cells

Deregulation of circular RNAs (circRNAs) is frequent in human glioma. Although circRNA ATPase phospholipid transporting 8B4 (circATP8B4) is highly expressed in glioma, its precise action in glioma development is still not fully understood. The relationship of microRNA (miR)-31-5p and circATP8B4 or nestin (NES) was predicted by bioinformatic analysis and confirmed by RNA pull-down and Dual-luciferase reporter assays. CircATP8B4, miR-31-5p and NES were quantified by qRT-PCR or western blot. Cell functional behaviors were assessed by EdU, wound-healing and transwell invasion assays. Xenograft model experiments were performed to define circATP8B4's activity in vivo. CircATP8B4, a true circular transcript, was upregulated in human glioma. CircATP8B4 downregulation weakened glioma cell growth, motility, and invasion and facilitated radiosensitivity. Mechanistically, circATP8B4 and NES 3'UTR harbored a shared miR-31-5p pairing site, and circATP8B4 involved the post-transcriptional NES regulation by functioning as a competing endogenous RNA (ceRNA). Furthermore, the miR-31-5p/NES axis participated in circATP8B4's activity in glioma cell proliferation, motility, invasion and radiosensitivity. Additionally, circATP8B4 loss diminished tumor growth and enhanced the anticancer effect of radiotherapy in vivo. We have uncovered an uncharacterized ceRNA cascade, circATP8B4/miR-31-5p/NES axis, underlying glioma development and radiosensitivity. Targeting the ceRNA crosstalk may have potential to improve the outcome of glioma patients.