Malignant Glioma account for the largest class of primary brain tumor, and its high malignant degree, therapy resistance and high recurrence rate are widely accepted to be caused by existence of glioma stem-like cells (GSCs). But the mechanisms underlying GSCs maintain are not completely clear. Recent evidences have shown that circular RNAs (circRNAs) are frequently dysregulated and play paramount roles in various cancers. circRNAs are abundant in central nervous system (CNS); however, few studies describe the clinical significance and role of circRNAs in gliomas, In our preliminary study, we used a vitro differentiation model upon inducing human neural progenitor cells (hNPCs) to mature glia cells, and identified a circRNA, circHMGCS1 (hsa_circ_0072391), which was highly expressed in hNPCs but was gradually downregulated in mature glia cells. In this study, we found that circHMGCS1 was inversely elevated in gliomas, and was positively correlated with malignant degree (III+IV vs I +II, P<0.05). Next, we verified that circHMGCS1 enhanced formation of neurosphere, and leaded to the resistance to TMZ treatment in vitro. Furthermore, we proved that circHMGCS1 could maintain the protein level of stemness relative transcription factor SOX2. RNA binding protein HuR, which was reported to stabilize the SOX2 mRNA, could be pulled down by circHMGCS1 in our ChIRP-MS assay. Inhibition of circHMGCS1 could partly decrease the binding of HuR with SOX2 mRNA 3’UTR. Finally, silencing of circHMGCS1 significantly inhibited formation of xenograft brain tumors and increased mice overal survival time in vivo. Taken together, our findings suggest that circHMGCS1 is a critical player in maintaining the stemness of GSCs via stablilized SOX2 by strengthening its interaction with RNA binding protein HuR. Therefore, we suggest that circHMGCS1 may serve as a new biomarker and therapeutic target for treatment of gliomas.

Citation Format: Jiehua He, Zuoyu Huang, Dong Yin. CircHMGCS1 interacts with RNA binding protein HuR and maintains stem-like cells in gliomas [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3788.