The Role of N6-Methyladenosine in Inflammatory Diseases

Abstract

N⁶-Methyladenosine (m⁶A) is the most abundant epigenetic RNA modification in eukaryotes, regulating RNA metabolism (export, stability, translation, and decay) in cells through changes in the activity of writers, erasers, and readers and ultimately affecting human life or disease processes. Inflammation is a response to infection and injury in various diseases and has therefore attracted significant attention. Currently, extensive evidence indicates that m⁶A plays an essential role in inflammation. In this review, we focus on the mechanisms of m⁶A in inflammatory autoimmune diseases, metabolic disorder, cardio-cerebrovascular diseases, cancer, and pathogen-induced inflammation, as well as its possible role as targets for clinical diagnosis and treatment.

Figure 1

The processes of RNA m⁶A methylation, demethylation, and regulation. m⁶A is read by readers and regulates almost all RNA activities, such as splicing, export, translation, decay, and stabilization.

Figure 2

Inflammatory pathways mainly include MAPK pathway, JAK/STAT pathway, and PI3K/AKT pathway.

Figure 3

The role of m6A in (a–d) inflammatory autoimmune diseases, (e, f) metabolic disorder, and (g, h) cardio-cerebrovascular diseases: (a) multiple sclerosis (MS); (b) inflammatory bowel disease (IBD); (c) systemic lupus erythematosus (SLE); (d) rheumatoid arthritis (RA); (e) obesity; (f) nonalcoholic fatty liver disease (NAFLD); (g) ischemic stroke (IS); (h) atherosclerosis (AS).

Figure 4

Cancer is regulated by m⁶A and the inflammatory microenvironment. In (a) lung adenocarcinoma and (b) human liver cancer, m⁶A modification regulates the expression of the target inflammatory gene. (c) Microenvironment inside the cancer and (d) numerous cytokines, such as IL-1β and IL-6, modulate the inflammatory microenvironment to stimulate tumor growth and invasion. (e) m⁶A application and targeting therapy in cancer through the inflammatory microenvironment.