CD 36: Focus on Epigenetic and Post-Transcriptional Regulation

Abstract

CD36 is a transmembrane protein involved in fatty acid translocation, scavenging for oxidized fatty acids acting as a receptor for adhesion molecules. It is expressed on macrophages, as well as other types of cells, such as endothelial and adipose cells. CD36 participates in muscle lipid uptake, adipose energy storage, and gut fat absorption. Recently, several preclinical and clinical studies demonstrated that upregulation of CD36 is a prerequisite for tumor metastasis. Cancer metastasis-related research emerged much later and has been less investigated, though it is equally or even more important. CD36 protein expression can be modified by epigenetic changes and post-transcriptional interference from non-coding RNAs. Some data indicate modulation of CD36 expression in specific cell types by epigenetic changes via DNA methylation patterns or histone tails, or through miRNA interference, but this is largely unexplored. The few papers addressing this topic refer mostly to lipid metabolism-related pathologies, whereas in cancer research, data are even more scarce. The aim of this review was to summarize major epigenetic and post-transcriptional mechanisms that impact CD36 expression in relation to various pathologies while highlighting the areas in need of further exploration.

The Multifunctionality of CD36 in Diabetes Mellitus and Its Complications—Update in Pathogenesis, Treatment and Monitoring

“…It has a hairpin-like structure and contains two transmembrane domains, a large highly glycosylated extracellular loop containing ligand-binding sites, and two short intracellular domains at C and N terminals [ 42 ]. Various molecular mechanisms for regulating CD36 gene expression [ 43 , 44 , 45 ] and posttranslational modifications [ 42 ] are responsible for the multiplicity of interactions and functional diversity of CD36. The regulatory mechanisms of the CD36 gene transcription involves interactions with several transcriptional factors: CCAAT/enhancer-binding protein (C/EBP) [ 46 ], peroxisome proliferator-activated receptor (PPAR) [ 47 ], and activating transcription factor 2 (ATF2) [ 48 ].…”

CD36 and CD97 in Pancreatic Cancer versus Other Malignancies

“…CD36 protein expression can be modified in metastasis via epigenetic modifications and post-transcriptional interference of non-coding RNA, as was recently suggested. As such, in certain cell types, regulation of CD36 expression involved DNA methylation or histone tails or miRNA interference [48].…”

New molecular basis associated with CD36‐negative phenotype in the sub‐Saharan African population

“…More than 20 sites of polymorphism in the coding sequence of the CD36 gene are known to lead to Type I deficiency, in a homozygous or compound heterozygous way. 4,9,10,12 The most frequent mutations are c.975T>G in African, c.268C>T and c.329_330del in Japanese, and c.329_330del and c.1228_1239del in Chinese populations. In a study by Lo et al, 19 the population in three classes of CD36 expression was classified-CD36 WT , CD36 low , and CD36 null , depending on their level of expression-and they tried to make a correlation with CD36 genetic variations: for two of four patients with Type I CD36 deficiencies (CD36 null ) they observed only one mutated allele, whereas the two other cases were, as commonly described, homozygous or compound heterozygous.…”

“…3 The CD36 protein consists of 472 amino acids with a molecular weight from 78 kDa to 88 kDa, according to the cell type and posttranslational modifications. 4,5 The CD36-negative (CD36neg) phenotype is only found in 0.3% of Caucasians, but is more common in African (2.5%-7%) or Asian populations (3%-11%) and appears to be asymptomatic. 6,7 The GP may be absent either on both PLTs and monocytes (Type I) or on PLTs alone (Type II).…”

“…8 Mutations leading to Type I deficiency are better described than mutations leading to Type II deficiency. 4,[9][10][11][12] The most common mutation leading to Type I deficiency is C268T (50% of the mutated alleles in Asian population), followed by 949insA and 329-330del AC. The mutations are homozygous or compound heterozygous, and both alleles must be inactivated.…”