Circular RNA VPS18 Promotes Glioblastoma Progression by Regulating miR-1229-3p/BCAT1 Axis.

Abstract

Circular RNAs (circRNAs) have been verified to play important roles in malignant tumors, including glioblastoma. The aim of this study is to explore the biological roles and underlying mechanisms of circRNA vacuolar protein sorting 18 homolog (circVPS18) in glioblastoma. A quantitative real-time polymerase chain reaction (qRT-PCR) was performed to measure the expression of circVPS18, microRNA (miR)-1299-3p, and branched-chain amino acid transaminase 1 (BCAT1). In vitro experiments were conducted using 5-ethynyl-2'-deoxyuridine (EdU), flow cytometry, transwell, and tube formation assays, respectively. Western blot was conducted to examine all protein levels. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were employed to confirm the interaction between miR-1229-3p and circVPS18 or BCAT1. The murine xenograft model was established to conduct in vivo assay. CircVPS18 and BCAT1 were highly expressed while miR-1229-3p was lowly expressed in glioblastoma tissues and cells. CircVPS18 knockdown inhibited glioblastoma progression by inhibiting cell proliferation, migration, invasion, and angiogenesis, and promoting cell apoptosis. Moreover, miR-1229-3p could be targeted by circVPS18; inhibition of miR-1229-3p could invert the suppressive effect of circVPS18 knockdown on glioblastoma tumorigenesis. Furthermore, BCAT1 was a target of miR-1229-3p; functionally, BCAT1 overexpression could reverse the inhibitory effects of miR-1229-3p upregulation on glioblastoma cell malignant phenotypes. Moreover, we also verified that circVPS18A could regulate BCAT1 expression by sponging miR-1229-3p. Additionally, circVPS18 silencing also restrained tumor growth and metastasis in vivo. CircVPS18 accelerated glioblastoma progression by miR-1229-3p/BCAT1 axis, providing a potential therapeutic target for glioblastoma.