SOX4 Mediates ATRA-Induced Differentiation in Neuroblastoma Cells

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.

METTL14-Mediate the Biological Effects of EMT in Bladder Cancer Cells by Methylating SOX4 mRNA with m6A

“…25 At the same time, SOX4 can mediate the differentiation of neuroblastoma induced by ATRA. 26 SOX4 is an important downstream molecule of METTL14-targeted m6A modification. 6,11 This study unveiled the role of METTL14-modified SOX4 in BC, thus expanding our understanding of the diverse molecular mechanisms governing METTL14 expression and enriching the current knowledge base on N6-methylation.…”

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

“…Figure 9B). Most of the candidates do not have known neutrophil-associated functions, but are associated with retinoic acid (RA) signaling, including suppression (alx4a, dlx4a, and sox9a/b) (35)(36)(37), activation (hmx1, sox4b, msx2b, hoxb2a, nr6a1a) (38)(39)(40)(41)(42) and serving as co-receptors (nr4a2b) (43). Altogether, we identified the state transition paths in zebrafish neutrophils compared to human neutrophils and identified TFs that potentially drive the deviations.…”

Pediatric Cancers: Insights and Novel Therapeutic Approaches

“…A dual HDAC and PI3K inhibitor CUDC-907 [10] and an ERK inhibitor Ulixertinib [11] were found to be effective treatment approaches for high-risk NB. Further, SOX4 is shown to mediate NB cell differentiation, and SOX4 knockdown partially reversed retinoic acid-induced differentiation in NB cells [12]. The LPA-LPAR1 axis is shown to have migration-inhibitory effects on NB cells, and knockdown of LPRA1 promotes NB cell migration and metastasis [13].…”