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image of The Involvement of the NEAT1-1/miR-873-5p/GalNAcT-I Axis in the Development of Neuroblastoma

Abstract

Background:

The most prevalent extracranial solid tumor in childhood is neuroblastoma (NB), which arises from undifferentiated neural crest cells. However, the prognosis of this condition remains unfavorable, and the underlying mechanisms of its origin are still elusive. Therefore, this study aimed to investigate the specific mechanism underlying NEAT1-1 in NB.

Methods:

In this study, the expressions of NEAT1-1, miR-873-5p, and GalNAcT-I were analyzed by real-time quantitative polymerase chain reaction (qRT-PCR) and Western blot (WB). Then, CCK-8 assays were conducted to evaluate the proliferation of NB cells. The Transwell assay was then performed to evaluate the invasion and migration of NB cells. Further, flow cytometry was utilized for the detection of cell apoptosis. Furthermore, the luciferase reporter gene assay was carried out to investigate the relationship between NEAT1-1 and miR-873-5p, as well as between miR-873-5p and GalNAcT-I. In contrast, an RNA-pull-down assay was conducted to confirm the regulatory relationship between NEAT1-1 and miR-873-5p. The effect of NEAT1-1 on tumor growth was detected in the BALB/c nude mice model.

Results:

The qRT-PCR analysis revealed a significantly upregulated expression of NEAT1-1 in NB tumors compared to adjacent non-tumor tissue specimens. Suppression of NEAT1-1 resulted in the inhibition of tumor characteristics and induction of apoptosis in NB cells through the targeted regulation of miR-873-5p. Moreover, NEAT1-1 exerted its regulatory effect on GalNAcT-I protein levels by acting as a sponge for miR-873-5p in NB cells. Importantly, the downregulation of NEAT1-1 effectively suppressed tumor growth .

Conclusion:

Collectively, our findings suggest that the down-regulation of NEAT1-1 exerts a suppressive effect on NB progression by modulating the miR-873-5p/GalNAcT-I pathway, thereby providing novel insights into elucidating the underlying mechanisms of NB.

This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: https://creativecommons.org/licenses/by/4.0/legalcode. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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2025-01-27
2025-02-10
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  • Article Type:
    Research Article
Keywords: Proliferation ; Apoptosis ; NEAT1-1 ; MiR-873-5p ; GalNAcT-I ; Neuroblastoma
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