Circ-CUX1 Accelerates the Progression of Neuroblastoma via miR-16-5p/DMRT2 Axis

Circular RNAs (circRNAs) played pivotal roles in the initiation and progression of cancers. CircRNA cut like homeobox 1 (circ-CUX1; hsa_circ_0132813) has been reported to contribute to neuroblastoma (NB) development by previous study. Furthermore, previous works reported that microRNA-16-5p (miR-16-5p) was down-regulated while doublesex and mab-3 related transcription factor 2 (DMRT2) was up-regulated in NB. The interaction and functional association between miR-16-5p and circ-CUX1 or DMRT2 were investigated in this study. Cell proliferation, cell cycle progression, colony formation, migration and invasion of NB cells were examined by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, flow cytometry, colony formation assay and transwell migration and invasion assays. The glycolysis was analyzed through measuring the consumption of glucose and the production of lactate and ATP. Dual-luciferase reporter assay, RNA immunoprecipitation (RIP) assay and RNA-pull down assay were utilized to confirm the interaction between miR-16-5p and circ-CUX1 or DMRT2. Tumor xenograft assay was performed to explore the function of circ-CUX1 in xenograft tumor growth in vivo. Circ-CUX1 promoted the proliferation, migration, invasion and glycolysis of NB cells. miR-16-5p was a direct target of circ-CUX1, and miR-16-5p overexpression-mediated effects in NB cells were partly alleviated by the introduction of circ-CUX1 overexpression plasmid. DMRT2 was a target of miR-16-5p in NB cells, and the introduction of anti-miR-16-5p overturned the influences of DMRT2 interference on the proliferation, migration and invasion and glycolysis of NB cells. Circ-CUX1 silencing restrained xenograft tumor growth in vivo. In conclusion, circ-CUX1 accelerated the proliferation, migration, invasion and glycolysis of NB cells through targeting miR-16-5p/DMRT2 signaling cascade.