Peroxisome Proliferator-Activated Receptor Gamma in Obesity and Colorectal Cancer: the Role of Epigenetics.

ABSTRACT: Peroxisome proliferator-activated receptor gamma (PPAR?) is a nuclear receptor that is deregulated in obesity. PPAR? exerts diverse antineoplastic effects. Attempting to determine the clinical relevance of the epigenetic mechanisms controlling the expression PPAR? and susceptibility to colorectal cancer (CRC) in obese subjects, this study investigated the role of some microRNAs and DNA methylation on the deregulation of PPAR?. Seventy CRC patients (34 obese and 36 lean), 22 obese and 24 lean healthy controls were included. MicroRNA levels were measured in serum. PPAR? promoter methylation was evaluated in peripheral blood mononuclear cells (PBMC). PPAR? level was evaluated by measuring mRNA level in PBMC and protein level in serum. The tested microRNAs (miR-27b, 130b and 138) were significantly upregulated in obese and CRC patients. Obese and CRC patients had significantly low levels of PPAR?. A significant negative correlation was found between PPAR? levels and the studied microRNAs. There was a significant PPAR? promoter hypermethylation in CRC patients that correlated to low PPAR? levels. Our results suggest that upregulation of microRNAs 27b, 130b and 138 is associated with susceptibility to CRC in obese subjects through PPAR? downregulation. Hypermethylation of PPAR? gene promoter is associated with CRC through suppression of PPAR? regardless of BMI.

SUBMITTER: Motawi TK 

PROVIDER: S-EPMC5587696 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature