HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Circ-CREBBP promotes cell tumorigenesis and glutamine catabolism in glioma by regulating miR-375/glutaminase axis.

Abstract
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.
AuthorsLintao Zhang, Lin Ye, Zengliang Xu, Yanfei Jin, Dewen Song
JournalBrain research (Brain Res) Vol. 1775 Pg. 147730 (01 15 2022) ISSN: 1872-6240 [Electronic] Netherlands
PMID34813772 (Publication Type: Journal Article)
CopyrightCopyright © 2021. Published by Elsevier B.V.
Chemical References
  • MicroRNAs
  • RNA, Circular
  • Glutamine
  • CREB-Binding Protein
  • Glutaminase
Topics
  • Brain Neoplasms (genetics, metabolism, mortality)
  • CREB-Binding Protein (genetics, metabolism)
  • Carcinogenesis (genetics)
  • Cell Proliferation (physiology)
  • Female
  • Gene Expression Regulation, Neoplastic
  • Glioma (genetics, metabolism, mortality)
  • Glutaminase (metabolism)
  • Glutamine (metabolism)
  • Humans
  • Male
  • MicroRNAs (genetics, metabolism)
  • Middle Aged
  • RNA, Circular (genetics, metabolism)
  • Survival Rate

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: