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Histone Deacetylase HDAC2 Regulates MicroRNA-125a Expression in Neuroblastoma

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Journal Brain Behav
Specialty Psychology
Date 2022 Jan 21
PMID 35060363
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Abstract

Background: Neuroblastoma (NB) is an infrequent childhood malignancy of the peripheral sympathetic nervous system and is accountable for about 10% of pediatric tumors. microRNA (miR)-125a has been implicated to serve as a tumor suppressor in various cancers. Herein, we set out to ascertain whether miR-125a exerts antitumor effects in NB.

Methods: Downregulated miRNAs were identified by miRNA microarray analysis of NB tissues and paracancerous tissues. The expression of miR-125a in NB tissues and cells was detected by reverse transcription-quantitative (RT-q) PCR, followed by prognostic analysis. Gene Ontology (GO) enrichment analysis was performed on target genes of differentially expressed miRNAs. Cell proliferation, apoptosis, and differentiation were detected by cell counting kit-8 (CCK-8), Hoechst staining, immunofluorescence, and western blot. NB cells were injected into nude mice to detect tumorigenic, apoptotic, and differentiation activities in vivo. Dual-luciferase assay and chromatin immunoprecipitation (ChIP) were carried out to verify the binding relationship between miR-125a and PHOX2B or histone deacetylases 2 (HDAC2), respectively. Finally, rescue experiments were conducted.

Results: miR-125a was downregulated in NB tissues and cells, which was associated with poor prognosis. miR-125a reduced NB cell proliferation and augmented apoptosis and differentiation. NB cells with miR-125a overexpression decreased cell tumorigenesis and increased apoptosis and differentiation in xenograft tumor tissues. miR-125a targeted PHOX2B, which was highly expressed in NB tissues and cells. HDAC2, highly expressed in NB tissues and cells, repressed miR-125a transcription through histone deacetylation. Overexpression of HDAC2 or PHOX2B rescued the effects of miR-125a on NB cell proliferation, apoptosis, and differentiation.

Conclusion: HDAC2 inhibited miR-125a transcription through deacetylation, and miR-125a suppressed NB development through binding to PHOX2B.

Citing Articles

HDAC2 as a target for developing anti-cancer drugs.

Jo H, Shim K, Kim H, Jung H, Jeoung D Comput Struct Biotechnol J. 2023; 21:2048-2057.

PMID: 36968022 PMC: 10030825. DOI: 10.1016/j.csbj.2023.03.016.


Histone deacetylase HDAC2 regulates microRNA-125a expression in neuroblastoma.

Liu D, Tang X, Huang Z, Wen J, Zhou Y Brain Behav. 2022; 12(2):e2401.

PMID: 35060363 PMC: 8865159. DOI: 10.1002/brb3.2401.

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