Rabbit Anti-Human RELA (Acetyl-Lys310) polyclonal antibody

Purpose The ceramide pathway is strongly associated with the regulation of tumor proliferation, differentiation, senescence, and apoptosis. This study aimed to explore the gene signatures, prognostic value, and immune-related effects of ceramide-regulated genes in lung adenocarcinoma (LUAD). Methods Public datasets of LUAD from The Cancer Genome Atlas and Gene Expression Omnibus were selected. Consensus clustering was adopted to classify LUAD patients, and a least absolute shrinkage and selection operator (LASSO) regression model was employed to develop a prognostic risk signature. CIBERSORT algorithm was used to estimate the association between the risk signature and the tumor immune microenvironment. Results Most of the 22 ceramide-regulated genes were differentially expressed between LUAD and normal samples. LUAD patients were classified into two subgroups (cluster 1 and 2) and cluster 2 was associated with a poor prognosis. Furthermore, a prognostic risk signature was developed based on the three ceramide-regulated genes, Cytochrome C (CYCS), V-rel reticuloendotheliosis viral oncogene homolog A (RELA) and Fas-associated via death domain (FADD). LUAD patients with low- and high-risk scores differed concerning the subtypes of tumor-infiltrating immune cells. A moderate to weak correlation was observed between the risk score and tumor-infiltrating immune cells. Conclusions Ceramide-regulated genes could predict clinical prognostic risk and affect the tumor immune microenvironment in LUAD.

It was shown that in the presence of the recombinant protein YB-1, the response of human leukemic monocytes THP-1 to stimulation with muramylpeptide GMDP and LPS was significantly reduced, which was manifested in a decrease of the relative content of mRNA encoding the following molecules: proinflammatory cytokine IL-1 beta, innate immunity receptors NOD2 and TLR4, their adapters RIP2 and MyD88, and the p105/p50 (NF-kappa B1) and p100/p52 (NF-kappa B2) subunits of the NF-kappa B transcription factor. The inhibiting effect of YB-1 protein also follows from the lower level of p65 protein (RelA NF-kB) in nuclei of cells stimulated with LPS and GMDP/LPS. Inactivation of the NOD2 gene in the THP-1 cells resulted in a decrease of IL-1 beta mRNA in response to GMDP, LPS, and GMDP/LPS. At the same time, inactivation of the YB-1 gene led to an increased relative content of IL-1 beta and other molecules' mRNA upon stimulation with GMDP. However, in response to stimulation with LPS and GMDP/LPS the level of IL-1 beta mRNA decreased in comparison to the initial cells, which indicates that YB-1 is necessary for the induction of an optimal immune response. Thus, the data obtained indicate the involvement of YB-1 in the innate immunity receptor system as a negative regulator of NOD2 receptor activity.