Silencing of circular RNA circPDE5A suppresses neuroblastoma progression by targeting the miR-362-5p/NOL4L axis.

Abstract

OBJECTIVE:

Neuroblastoma (NB) is the most common extra-cranial solid tumour in early childhood. Circular RNAs (circRNAs) have been implicated in the development of NB. The purpose of the current study was to explore the molecular action of circRNA phosphodiesterase 5 A (circPDE5A) in NB malignant progression.

MATERIALS AND METHODS:

The expression levels of circPDE5A, miR-362-5p and nucleolar protein 4 like (NOL4L) were assessed by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. Cell proliferation was detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTS) assay. Cell migration and invasion were evaluated by transwell assay. The levels of glucose consumption and lactate production were measured using the commercial assay kits. Targeted correlations among circPDE5A, miR-362-5p and NOL4L were confirmed by dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. In vivo assays were performed to examine the role of circPDE5A in tumour growth in vivo.

RESULTS:

Our results revealed that circPDE5A was up-regulated in NB tissues and cells. The silencing of circPDE5A suppressed NB cell proliferation, migration, invasion, and glycolysis in vitro and diminished tumour growth in vivo. Moreover, circPDE5A directly targeted miR-362-5p by binding to miR-362-5p. CircPDE5A silencing impeded NB malignant progression in vitro through up-regulating miR-362-5p. Furthermore, NOL4L was a direct target of miR-362-5p, and NOL4L mediated the regulation of miR-362-5p on NB malignant progression in vitro. Additionally, circPDE5A functioned as a regulator of NOL4L expression via targeting miR-362-5p.

CONCLUSIONS:

Our current findings identified that the knockdown of circPDE5A suppressed NB malignant progression at least in part by the regulation of the miR-362-5p/NOL4L axis, providing a novel rationale for developing circPDE5A as a potential target for NB management.

• Authors: Yongcun Chen, Liangfeng Lin, Xiaohao Hu, Qiaoyu Li, Min Wu
• Journal: The International journal of neuroscience (Int J Neurosci) Vol. 133 Issue 2 Pg. 141-151 (Feb 2023) ISSN: 1563-5279 [Electronic] England
• PMID: 33635749 (Publication Type: Journal Article)

Chemical References

• RNA, Circular
• Bromides
• MicroRNAs
• NOL4L protein, human
• Proteins
• MIRN362 microRNA, human

Topics

• Child, Preschool
• Humans
• RNA, Circular (genetics)
• Neuroblastoma
• Blotting, Western
• Bromides
• Cell Proliferation (genetics)
• MicroRNAs (genetics)
• Gene Expression Regulation, Neoplastic
• Cell Line, Tumor
• Proteins