Circ-CUX1 Accelerates the Progression of Neuroblastoma via miR-16-5p/DMRT2 Axis
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ORIGINAL PAPER
Circ‑CUX1 Accelerates the Progression of Neuroblastoma via miR‑16‑5p/DMRT2 Axis Xiao Zhang1 · Jian Zhang1 · Qian Liu1 · Yuehua Zhao1 · Wenhua Zhang1 · Haiyan Yang1 Received: 16 April 2020 / Revised: 10 September 2020 / Accepted: 12 September 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract 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 miR16-5p 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. Keyword Neuroblastoma (NB) · circ-CUX1 · miR-16-5p · DMRT2 Abbreviations circRNAs Circular RNAs DMRT2 Doublesex and mab-3 related transcription factor 2 circ-CUX1 CircRNA cut like homeobox 1 NB Neuroblastoma miR-16-5p MicroRNA-16-5p
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s11064-020-03132-w) contains supplementary material, which is available to authorized users. * Haiyan Yang [email protected] 1
Department of Pediatric, Affiliated Hospital of Weifang Medical University, Kuiwen District, No.4948, Shengli East Street, 261000 Weifang, Shandong Province, China
Introduction Neuroblastoma (NB) is a malignant tumor originated from primitive neural crest, and it is one of the most common childhood cancers. NB patients are in an advanced stage at the time of d
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