Crosstalk Between Inflammatory Signaling and Methylation in Cancer

Abstract

Inflammation is an intricate immune response against infection and tissue damage. While the initial immune response is important for preventing tumorigenesis, chronic inflammation is implicated in cancer pathogenesis. It has been linked to various stages of tumor development including transformation, proliferation, angiogenesis, and metastasis. Immune cells, through the production of inflammatory mediators such as cytokines, chemokines, transforming growth factors, and adhesion molecules contribute to the survival, growth, and progression of the tumor in its microenvironment. The aberrant expression and secretion of pro-inflammatory and growth factors by the tumor cells result in the recruitment of immune cells, thus creating a mutual crosstalk. The reciprocal signaling between the tumor cells and the immune cells creates and maintains a successful tumor niche. Many inflammatory factors are regulated by epigenetic mechanisms including DNA methylation and histone modifications. In particular, DNA and histone methylation are crucial forms of transcriptional regulation and aberrant methylation has been associated with deregulated gene expression in oncogenesis. Such deregulations have been reported in both solid tumors and hematological malignancies. With technological advancements to study genome-wide epigenetic landscapes, it is now possible to identify molecular mechanisms underlying altered inflammatory profiles in cancer. In this review, we discuss the role of DNA and histone methylation in regulation of inflammatory pathways in human cancers and review the merits and challenges of targeting inflammatory mediators as well as epigenetic regulators in cancer.

Epigenetic Regulation of Inflammatory Signaling and Inflammation-Induced Cancer

“…Aside from these two histone modifications, histone phosphorylation and ubiquitination have also gradually gained attention for their crucial roles in regulating transcription and chromatin structure. As the roles of histone and DNA methylation/demethylation in cancer and inflammation have been recently and extensively reviewed ( Das et al, 2021 ), here we focus on the mechanistic basis of histone acetylation/deacetylation, phosphorylation and ubiquitination, and how they mediate inflammatory signaling in cancer.…”

Epigenetic Network in Immunometabolic Disease

“…JMJD3 is involved in the regulation of macrophage polarization, with its expression are higher in M1‐polarized macrophages compared to M2‐polarized macrophages. [ 106 ] HDAC3 controls the regulation of inflammatory genes in macrophages, while histone deacetylase 2 (HDAC2) contributes to the resolution of inflammation. [ 107 ] In monocytes isolated from T1DM and T2DM patients, acetylation of H3 at the promoter of TNF and COX2 genes was increased, whereas H3K4 mono‐methylation contributes to monocyte dysfunction in T2DM patients by inducing transcription of NF‐kBp65 and proinflammatory genes like VCAM‐1, ICAM‐1, and MCP‐1.…”

Identification of TMEM178 as a Potential Prognostic Biomarker and Therapeutic Target for Breast Cancer

“…Transmembrane protein 178 (TMEM178, also known as TMEM178A), a member of the TMEM family, is located on chromosome 2p22.1. Previous studies showed the production and accumulation of pro-inflammatory cytokines, and the imbalance of calcium level are important factors to stimulate the progress of cancer ( 5 , 6 ). TMEM178 reduced the STIM1 puncta formation and the production of inflammatory cytokines IL-6, IL-1 β and TNF α, resulting in impairment of inflammatory response in cancer ( 7 , 8 ).…”