Circular RNA CREB-binding protein (circ-CREBBP) has been reported to involve in the
tumorigenesis of
glioma. However, the role and underlying molecular mechanism of circ-CREBBP in
glioma glutamine catabolism remain unclear. The expression of circ-CREBBP,
microRNA (miR)-375 and
glutaminase (GLS) was detected using quantitative real-time polymerase chain reaction and western blot. The 3‑(4, 5‑dimethylthiazol‑2‑y1)‑2, 5‑diphenyl tetrazolium
bromide (MTT), colony formation, flow cytometry and transwell assays were used to determine the effects of them on
glioma cell malignant
biological behaviors in vitro.
Glutamine metabolism was analyzed using assay kits. Murine xenograft model was established to investigate the role of circ-CREBBP in vivo. The binding interactions between miR-375 and circ-CREBBP or GLS were confirmed by the dual-
luciferase reporter assay. Circ-CREBBP was highly expressed in
glioma tissues and cells, and high expression of circ-CREBBP predicted poor prognosis. Circ-CREBBP knockdown suppressed cell proliferation, migration, invasion and
glutamine metabolism while expedited cell apoptosis in
glioma in vitro, as well as impeded
tumor growth in vivo. Circ-CREBBP directly targeted miR-375, which was demonstrated to restrain
glioma cell growth, motility and
glutamine metabolism. Moreover, miR-375 inhibition reverted the anticancer effects of circ-CREBBP knockdown on
glioma cells. GLS was a target of miR-375, GLS silencing or the treatment of GLS inhibitor bis-2-(5-phenylacetamido-1,3,4-thiadiazol-2-yl)ethyl
sulfide (BPTES) impaired
glioma cell malignant phenotypes and
glutamine metabolism. Importantly, GLS up-regulation weakened the
tumor-suppressive functions of miR-375 on
glioma cells. Mechanistically, circ-CREBBP indirectly regulated GLS expression through sponging miR-375. In all, circ-CREBBP expedited
glioma tumorigenesis and
glutamine metabolism through miR-375/GLS axis, suggesting a promising target for combined
glioma therapy.