====== circASAP1 ======

Acquired [[chemoresistance]] is a major challenge in the clinical treatment of [[glioblastoma]] (GBM). Circular RNAs have been verified to play a role in tumor chemoresistance. However, the underlying mechanisms remain unclear. The aim of s study was to elucidate the potential role and molecular mechanism of circASAP1 in temozolomide resistance of GBM.

Weiet al. analyzed [[circRNA]] alterations in recurrent GBM tissues relative to primary GBM through RNA sequencing. Real-time quantitative reverse transcription PCR (qRT-PCR) verified the expression of circASAP1 in tissues and cells. Knockdown and overexpressed plasmids were used to evaluate the effect of circASAP1 on GBM cell proliferation and temozolomide-induced apoptosis. Mechanistically, [[Fluorescence in situ hybridization]], [[dual-luciferase reporter]], and RNA immunoprecipitation assays were performed to confirm the regulatory network of circASAP1/miR-502-5p/NRAS. Intracranial tumors model was used to verify our findings in vivo.

Results: CircASAP1 expression was significantly up-regulated in recurrent GBM tissues and temozolomide-resistant cell lines. CircASAP1 overexpression enhanced GBM cell proliferation and temozolomide-resistance, which could reduced by circASAP1 knockdown. Further experiments revealed that circASAP1 increasd the expression of NRAS via sponging miR-502-5p. Moreover, circASAP1 depletion effectively restored the sensitivity of temozolomide-resistant xenografts to temozolomide treatment in vivo.

Conclusions: Our data demonstrate that circASAP1 exerts regulatory functions in GBM and that ceRNA-mediated microRNA sequestration might be a potential therapeutic strategy for GBM treatment
((Wei Y, Lu C, Zhou P, et al. EIF4A3-induced circular RNA ASAP1(circASAP1) promotes tumorigenesis and temozolomide resistance of glioblastoma via NRAS/MEK1/ERK1/2 signaling [published online ahead of print, 2020 Sep 14]. Neuro Oncol. 2020;noaa214. doi:10.1093/neuonc/noaa214)).