Ann Surg Treat Res.  2024 May;106(5):284-295. 10.4174/astr.2024.106.5.284.

Effects of transcription factor SOX11 on the biological behavior of neuroblastoma cell and potential regulatory mechanism

• Huang JR
• Li Y
• Chen P
• Wei JX
• Yang X
• Xu QQ
• Chen JB

• KMID: 2555725
• DOI: http://doi.org/10.4174/astr.2024.106.5.284

Abstract

Purpose
This study aimed to analyze the expression and prognosis of SRY-box transcription factor 11 (SOX11) in neuroblastoma (NB), as well as the biological function and potential regulatory mechanism of SOX11 in NB.
Methods
Public RNA sequencing was used to detect the expression level of SOX11. The Kaplan-Meier curve and hazard ratios (HR) were used to determine the prognostic value of SOX11 in NB. Functional analyses were performed using CCK8, wound healing assay, and transwell invasion assay. Finally, the potential target genes of SOX11 were predicted by Harmonizonme (Ma'ayan Laboratory) and Cistrome Data Browser (Cistrome Project) database to explore the potential molecular mechanism of SOX11 in NB.
Results
Compared with normal adrenal tissue, the expression of SOX11 in NB tissue was significantly upregulated. The Kaplan-Meier curve showed that high expression of SOX11 was associated with poor prognosis in children with NB (HR, 1.719; P = 0.049). SOX11 knockdown suppressed the migration capacity of SK-N-SH cells but did not affect proliferation and invasion capacity. Enhancer of zeste homolog 2 (EZH2) may be a potential downstream target gene for the transcription factor SOX11 to play a role in NB.
Conclusion
The transcription factor SOX11 was significantly upregulated in NB. SOX11 knockdown suppressed the migration capacity of NB cell SK-N-SH. SOX11 may promote the progression of NB by targeting EZH2.

Keyword

Cell migration inhibition; Enhancer of zeste homolog 2; Neuroblastoma; SOXC transcription factors

Figure

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  Fig. 1 The expression of SOX11. (A) Neuroblastoma (NB) tissue and adrenal gland tissue. (B) Receiver operating characteristics of SOX11. (C–F) Different age groups (C), risk groups (D), MYCN status groups (E), and histology groups (F) in NB tissue. SOX11, SRY-box transcription factor 11; mRNA, messenger RNA; TARGET, Therapeutically Applicable Research to Generate Effective Treatments database (https://ocg.cancer.gov/programs/target); TPR, true positive rate; FPR, false positive rate; AUC, area under the curve; CI, confidence interval. *P < 0.05, **P < 0.01, ***P < 0.001.

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  Fig. 2 Prognostic value of SOX11 in neuroblastoma. Hazard ratio, 1.719; 95 confidence interval, 0.798–1.963. SOX11, SRY-box transcription factor 11.

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  Fig. 3 Silencing SOX11 inhibited the migration of SK-N-SH. (A) Western blot confirmed the efficiency of the silencing. (B) Quantitative polymerase chain reaction confirmed the efficiency of the silencing. (C–E) Effect of silencing SOX11 on SK-N-SH migatory capability (C), SK-N-SH invasion capability (D), and the proliferative capacity of SK-N-SH (E). SOX11, SRY-box transcription factor 11; si, small interfering; NC, negative control; mRNA, messenger RNA; NS, no statistically significant difference. *P < 0.05; **P < 0.01; ***P < 0.001.

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  Fig. 4 Enrichment analysis of SOX11 co-expressed genes in neuroblastoma (NB). (A) Differentially expressed genes (DEGs) of NB. (B) Intersection Venn diagram of DEGs of NB and all transcription factors (TFs) of humans. (C) Biological processes. (D) Cellular components. (E) Molecular function. (F) Kyoto Encyclopedia of Genes and Genomes pathway. SOX11, SRY-box transcription factor 11; NS, not significant.

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  Fig. 5 Gene set enrichment analysis (GSEA) analysis. (A) GSEA analysis overall view. (B) Neuronal system. (C) Nervous system development. (D) Developmental biology. KEGG, Kyoto Encyclopedia of Genes and Genomes; NABA, network for analysis of biomedical acceleration matrisome; NES, normalized enrichment score; FDR, false discovery rate.

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  Fig. 6 SOX11 activates the expression of EZH2. (A) Intersection of target genes predicted by CHEA Transcription Factor Targets and Cistrome Data Browser (DB) with up-regulated differential genes (DEGs). (B) Binding peak of SOX11 and EZH2. (C) Expression of EZH2 in adrenal gland and neuroblastoma (NB). (D) Receiver operating characteristics of EZH2. (E) Correlation between SOX11 and EZH2 expression. SOX11, SRY-box transcription factor 11; EZH2, enhancer of zeste homolog 2; TARGET, Therapeutically Applicable Research to Generate Effective Treatments database; GTEx, Gene-Tissue Expression Project; TPR, true positive rate; FPR, false positive rate; AUC, area under the curve.

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