circCUX1 promotes neuroblastoma progression and glycolysis by regulating the miR-338-3p/PHF20 axis

Abstract

Neuroblastoma (NB) is an extracranial solid malignancy in childhood. More and more studies have demonstrated that circRNAs are essential regulators of various tumors. This study conducted to explore the role and mechanism of circular RNA CUT-like homeobox 1 (circCUX1) in NB. The levels of circCUX1, miR-338-3p and plant homeodomain finger protein 20 (PHF20) were detected by qRT-PCR or Western blot. Cell proliferation and apoptosis were evaluated by colony formation assay, flow cytometry and Western blot analysis. Cell migration and invasion were examined via transwell assay. Glycolysis was expressed by measuring the extracellular acidification rate (ECAR). The interaction among circCUX1, miR-338-3p and PHF20 were validated by dual-luciferase reporter assay and RNA Immunoprecipitation assay. Besides, xenograft experiment was performed to assess tumor growth in vivo. circCUX1 and PHF20 were up-regulated, while miR-338-3p was down-regulated in NB tissues and cells. Knockdown of circCUX1 suppressed the progression and glycolysis of NB cells. circCUX1 triggered NB progression and glycolysis by regulating miR-338-3p. Additionally, down-regulation of miR-338-3p promoted NB progression and glycolysis via targeting PHF20. Moreover, circCUX1 sponged miR-338-3p to regulate PHF20 expression. Furthermore, circCUX1 silencing hindered tumor growth in vivo. circCUX1 depletion suppressed tumor progression and glycolysis in NB by regulating miR-338-3p/PHF20 axis, suggesting a potential biomarker for NB treatment.