Noncoding RNAs and Macrophage Differentiation in Metabolic Diseases, Atherosclerosis, and Cancer - Abstract
Increased infiltration of monocytes in white adipose tissue, pancreas, liver, and arteries is the initial step in the pathogenesis of metabolic diseases, obesity, type 2 diabetes, non-alcoholic fatty liver diseases, and atherosclerosis. They tend to differentiate into M1 macrophages, associated with mitochondrial and endoplasmic reticulum oxidative stress, insulin resistance, and inflammation. Furthermore, many studies link metabolic diseases to an increased risk of several cancer types. However, tumor-associated macrophages are predominantly M2. Of interest, a cluster consisting of miR-17, miR-27a, miR-29a, miR-34a, miR125b, miR-130b, miR-140, miR-155, and miR-222 tend to be overexpressed in cardiometabolic tissues, inducing M1 macrophage polarization and immunemediated cell death. In contrast, they tend to be suppressed in tumors associated with M2 macrophage polarization and immunosuppression. Often LPS, inflammatory cytokines, leukotrienes, C-reactive protein, glucose, and oxidized LDL tend to upregulate these noncoding RNAs in metabolic and vascular tissues, while hypoxia, MYC, IFN-?, TGF-?, and lactate tend to downregulate them in tumors. However, a consistent study of the regulation of the proposed cluster related to stages in disease development is lacking.