» Articles » PMID: 36428735

SOX4 Mediates ATRA-Induced Differentiation in Neuroblastoma Cells

Overview
Journal Cancers (Basel)
Publisher MDPI
Specialty Oncology
Date 2022 Nov 26
PMID 36428735
Authors
Affiliations
Soon will be listed here.
Abstract

Neuroblastoma (NB), which is considered to be caused by the differentiation failure of neural crest cells, is the most common extracranial malignant solid tumor in children. The degree of tumor differentiation in patients with NB is closely correlated with the survival rate. To explore the potential targets that mediate NB cell differentiation, we analyzed four microarray datasets from GEO, and the overlapping down- or upregulated DEGs were displayed using Venn diagrams. SOX4 was one of the overlapping upregulated DEGs and was confirmed by RT-qPCR and Western blot in ATRA-treated NGP, SY5Y, and BE2 cells. To clarify whether SOX4 was the target gene regulating NB cell differentiation, the correlation between the expression of SOX4 and the survival of clinical patients was analyzed via the R2 database, SOX4 overexpression plasmids and siRNAs were generated to change the expression of SOX4, RT-qPCR and Western blot were performed to detect SOX4 expression, cell confluence or cell survival was detected by IncuCyte Zoom or CCK8 assay, immunocytochemistry staining was performed to detect cells' neurites, and a cell cycle analysis was implemented using Flow cytometry after PI staining. The results showed that the survival probabilities were positively correlated with SOX4 expression, in which overexpressing SOX4 inhibited NB cell proliferation, elongated the cells' neurite, and blocked the cell cycle in G1 phase, and that knockdown of the expression of SOX4 partially reversed the ATRA-induced inhibition of NB cell proliferation, the elongation of the cells' neurites, and the blocking of the cell cycle in the G1 phase. These indicate that SOX4 may be a target to induce NB cell differentiation.

Citing Articles

Single-cell Transcriptional Landscape of Temporal Neutrophil Response to Burn Wound in Larval Zebrafish.

Hou Y, Khatri P, Rindy J, Schultz Z, Gao A, Chen Z J Immunol. 2024; 213(4):469-480.

PMID: 38922186 PMC: 11300161. DOI: 10.4049/jimmunol.2400149.


SIRT5-Mediated Desuccinylation of RAB7A Protects Against Cadmium-Induced Alzheimer's Disease-Like Pathology by Restoring Autophagic Flux.

Deng P, Fan T, Gao P, Peng Y, Li J, Qin M Adv Sci (Weinh). 2024; 11(30):e2402030.

PMID: 38837686 PMC: 11321632. DOI: 10.1002/advs.202402030.


Single-cell transcriptional landscape of temporal neutrophil response to burn wound in larval zebrafish.

Hou Y, Khatri P, Rindy J, Schultz Z, Gao A, Chen Z bioRxiv. 2024; .

PMID: 38617269 PMC: 11014537. DOI: 10.1101/2024.04.01.587641.


Pediatric Cancers: Insights and Novel Therapeutic Approaches.

Agarwal S Cancers (Basel). 2023; 15(14).

PMID: 37509199 PMC: 10377340. DOI: 10.3390/cancers15143537.

References
1.
Chakraborty K, Kar S, Rai B, Bhagat R, Naskar N, Seth P . Copper dependent ERK1/2 phosphorylation is essential for the viability of neurons and not glia. Metallomics. 2022; 14(4). PMC: 8975716. DOI: 10.1093/mtomcs/mfac005. View

2.
Rajan J, Wang M, Marquis S, Chodosh L . Brca2 is coordinately regulated with Brca1 during proliferation and differentiation in mammary epithelial cells. Proc Natl Acad Sci U S A. 1996; 93(23):13078-83. PMC: 24049. DOI: 10.1073/pnas.93.23.13078. View

3.
Hatori Y, Yan Y, Schmidt K, Furukawa E, Hasan N, Yang N . Neuronal differentiation is associated with a redox-regulated increase of copper flow to the secretory pathway. Nat Commun. 2016; 7:10640. PMC: 4757759. DOI: 10.1038/ncomms10640. View

4.
Kim S, Volkl S, Ludwig S, Schneider H, Wixler V, Park J . Deficiency of Fhl2 leads to delayed neuronal cell migration and premature astrocyte differentiation. J Cell Sci. 2019; 132(6). DOI: 10.1242/jcs.228940. View

5.
Yoshikawa Y, Kimura S, Soga A, Sugiyama M, Ueno A, Kondo H . Plasmodium berghei Brca2 is required for normal development and differentiation in mice and mosquitoes. Parasit Vectors. 2022; 15(1):244. PMC: 9270840. DOI: 10.1186/s13071-022-05357-w. View