Identifying the p65-Dependent Effect of Sulforaphene on Esophageal Squamous Cell Carcinoma Progression via Bioinformatics Analysis

Abstract

Understanding the mechanism by which sulforaphene (SFE) affects esophageal squamous cell carcinoma (ESCC) contributes to the application of this isothiocyanate as a chemotherapeutic agent. Thus, we attempted to investigate SFE regulation of ESCC characteristics more deeply. We performed gene set enrichment analysis (GSEA) on microarray data of SFE-treated ESCC cells and found that differentially expressed genes are enriched in TNFα_Signaling_via_the_NFκB_Pathway. Coupled with the expression profile data from the GSE20347 and GSE75241 datasets, we narrowed the set to 8 genes, 4 of which (C-X-C motif chemokine ligand 10 (CXCL10), TNF alpha induced protein 3 (TNFAIP3), inhibin subunit beta A (INHBA), and plasminogen activator, urokinase (PLAU)) were verified as the targets of SFE. RNA-sequence (RNA-seq) data of 182 ESCC samples from The Cancer Genome Atlas (TCGA) were grouped into two phenotypes for GSEA according to the expression of CXCL10, TNFAIP3, INHBA, and PLAU. The enrichment results proved that they were all involved in the NFκB pathway. ChIP-seq analyses obtained from the Cistrome database indicated that NFκB-p65 is likely to control the transcription of CXCL10, TNFAIP3, INHBA, and PLAU, and considering TNFAIP3 and PLAU are the most significantly differentially expressed genes, we used chromatin immunoprecipitation-polymerase chain reaction (ChIP-PCR) to verify the regulation of p65 on their expression. The results demonstrated that SFE suppresses ESCC progression by down-regulating TNFAIP3 and PLAU expression in a p65-dependent manner.

Anti-inflammatory potential of digested Brassica sprout extracts in human macrophage-like HL-60 cells

“…46 Although the available literature about SFE interaction with anti-inflammatory pathways is not as large as that with SFN, this structural analog could also interact via the NF-κB pathway, which would result in a decrease in pro-inflammatory cytokine levels. 47 DIM is the condensation product of the dimerization of I3C, and also a hydrolysis derivate from indolic GSL glucobrassicin. In our previous work, treatment with DIM in the same LPS-stimulated HL-60 macrophage-like cell culture model reported a high anti-inflammatory activity against IL-6 production.…”

Single-cell transcriptomics of human cholesteatoma identifies an activin A-producing osteoclastogenic fibroblast subset inducing bone destruction

“…Our results are consistent with previous reports that INHBA expression is induced by IL-1β through the p38 MAPK and MEK/ERK pathways and by PGE 2 through the PKC and MEK/ERK pathways 22 . Furthermore, INHBA expression is induced by TNF-α through the NF-κB pathway 23,24 . The scRNA-seq data showed that CD45 − cells from cholesteatoma did not exhibit upregulation of IL-1β, PGE 2 synthase, or TNF-α, compared to skin fibroblasts (Supplementary Fig.…”