ALKB homolog 5 (ALKBH5)-induced circPUM1 upregulation facilitated the progression of neuroblastoma via miR-423–5p/PA2G4 axis

Abstract

BackgroundThe oncogenic role of circPUM1 has been revealed in multiple cancers. Nevertheless, the specific role and molecular mechanism of circPUM1 in neuroblastoma (NB) have never been reported. MethodsThe expression of genes was detected using RT-qPCR and Western Blot assay. The proliferation, migration, and invasion of NB cells were evaluated by CCK-8 and Transwell assays. Besides, mouse model was established to evaluate the effect of circPUM1 on the progression of NB. The interaction among genes was verified through RIP, MeRIP, or Luciferase reporter assay. ResultsThrough our investigation, it was discovered that circPUM1 expression was abnormally elevated in NB tissues and the abundance of circPUM1 was correlated with unfavorable clinical outcomes in NB patients. Besides, the viability and mobility of NB cells as well as NB tumor growth were suppressed by silencing circPUM1. Moreover, bioinformatics prediction and experimental verification demonstrated that circPUM1 was a sponge for miR-423–5p which further targeted proliferation-associated protein 2G4 (PA2G4). The oncogenic effect of circPUM1 on NB was exerted through suppressing miR-423–5p to elevate PA2G4 expression. Finally, we investigated the transcriptional factor causing the upregulation of circPUM1 in NB. The result was that ALKB homolog 5 (ALKBH5), an m6A demethylase, suppressed the m6A modification of circPUM1 and caused the elevation of circPUM1 expression in NB. ConclusionALKBH5 induced the upregulation of circPUM1 to accelerate the development of NB through regulating miR-423–5p/PA2G4 axis.