In silico analysis of expression and DNA methylation profiles of NLRP13 inflammasome in tumor cells

Abstract

BackgroundNOD-like receptor proteins (NLRs) are essential innate pattern recognition receptors that play fundamental roles in inflammation, and they have been associated with many cancers. NLRP13 (NLR Family Pyrin Domain Containing 13) belongs to the NLRP protein family, but its biological function is not as well defined as other related proteins in this family. Methods and resultsThe expression profile and CpG-aggregated methylation status of the NLRP13 gene were determined using GENT2 and TCGA online platforms. Samples from patients with different tumor stages were used to evaluate the promoter methylation status of NLRP13 in cancer versus normal tissues in a tumor stage-dependent manner by using UALCAN server. We further studied NLRP13 expression in response to inflammatory and hypomethylating agents in two distinct cancer cell lines, HT-29 (human colon adenocarcinoma) and C6 (rat glioma cells), following the treatment with LPS and/or a hypomethylating agent, decitabine, to reveal NLRP13 methylation profiles in these cell lines. ConclusionsUsing bioinformatics tools, we found that NLRP13 expression is higher in healthy breast, head and neck, prostate tissues compared to tumor tissues, whereas its expression is significantly higher in colorectal adenocarcinoma tissue than in normal colon tissue. We also found that NLRP13 gene is mostly hypomethylated in cancer tissues compared to normal tissues, and its high expression is linked with worse overall survival depending on cancer type. Based on data from UALCAN database, NLRP13 promoter methylation is similarly decreased in many cancer patients depending on individual cancer stages. Protein-protein interactions (PPIs) data indicated that NLRP13 showed a confidence interaction with MEFV, NLRC4 and CASP1 proteins, and gene ontology terms associated with functional partners of NLRP13 were also identified in the current study. Our results further showed that NLRP13 expression is regulated by DNA methylation, and treatment with decitabine might effect NLRP13-mediated inflammatory responses in cancer since LPS-induced pro-inflammatory responses specified by IL-1β, IL-18 and caspase-1 levels change in certain cases in cancer cell lines following the pretreatment with this epigenetic modulator. Our study is the first to provide evidence for the differential expression and epigenetic regulation of the NLPR13 in multiple cancer types.