SDC4 identified as an oncogenic target gene of NF-κB in TNFα-Induced tumor cells

Syndecan-4 (SDC4), a key member of the sulfated heparan sulfate proteoglycan (SDC) family, plays an important role in cell signaling. However, its function and regulatory mechanisms in tumors remain poorly understood. In this study, bioinformatic analysis revealed that SDC4 is significantly overexpressed in 16 types of tumors and positively correlated with poor prognosis in four types of these diseases. Knockdown of SDC4 inhibited tumor cell migration. Further analysis showed six transcription factors, including NF-κB, which potentially regulate SDC4 transcription. The UCSC Genome Browser database showed NF-κB binding peaks covered the SDC4 promoter in TNFα-stimulated tumor cells. ChIP-qPCR assay confirmed that TNFα treatment led to NF-κB binding at the SDC4 promoter, a genomic region also enriched for the active transcription mark H3K27Ac. qRT-PCR results demonstrated that TNFα treatment upregulated SDC4 in tumor cells. Immunofluorescence assay or qRT-PCR showed that the NF-κB inhibitor Bay11-7082 blocked TNFα-induced nuclear translocation of NF-κB, while both qRT-PCR and Western blot analyses showed Bay11-7082 could inhibit TNFα-induced upregulation of SDC4 at both mRNA and protein levels. Furthermore, SDC4 expression was positively correlated with NF-κB subunit RelA expression across 22 tumor types. In conclusion, this study identifies SDC4 as an oncogenic target gene of NF-κB, providing new insights for the development of anti-tumor therapies targeting the NF-κB pathway.