Epigenetic mechanisms linking obesity to colorectal cancer /
Noha Hussein Sayed
Epigenetic mechanisms linking obesity to colorectal cancer / الأليات فوق الوراثية التى تربط السمنة بسرطان القولون و المستقيم Noha Hussein Sayed ; Supervised Tarek Mohamed Kamal Motawi , Manal Fouad Ismail , Olfat Gamil Shaker - Cairo : Noha Hussein Sayed , 2018 - 132 P. : charts , facsimiles ; 25cm
Thesis (Ph.D.) - Cairo University - Faculty of Pharmacy - Department of Biochemistry
Peroxisome proliferator activated receptor gamma (PPARÞ) is a nuclear receptor that is deregulated in obesity. PPARÞ exerts diverse antineoplastic effects. Attempting to determine the clinical relevance of the epigenetic mechanisms controlling the expression PPARÞ and susceptibility to colorectal cancer (CRC) in obese subjects, this study investigated the role of some microRNAs and DNA methylation on the deregulation of PPARÞ. Seventy CRC patients (34 obese and 36 lean), 22 obese and 24 lean healthy controls were included. MicroRNA levels were measured in serum. PPARÞ promoter methylation was evaluated in blood. PPARÞ level was evaluated by measuring mRNA level in blood and protein level in serum. The tested microRNAs 27b, 130b and 138 were significantly upregulated in obese and CRC patients. Obese and CRC patients had significantly low levels of PPARÞ. A significant negative correlation was found between PPARÞ levels and the studied microRNAs. There was a significant PPARÞ promoter hypermethylation in CRC patients that correlated to low PPARÞ levels. Our results suggest that upregulation of microRNAs 27b, 130b and 138 is associated with susceptibility to CRC in obese subjects through PPARÞ downregulation. Hypermethylation of PPARÞ gene promoter is associated with CRC through suppression of PPARÞ regardless of BMI
Colorectal cancer Obesity PPARÞ
Epigenetic mechanisms linking obesity to colorectal cancer / الأليات فوق الوراثية التى تربط السمنة بسرطان القولون و المستقيم Noha Hussein Sayed ; Supervised Tarek Mohamed Kamal Motawi , Manal Fouad Ismail , Olfat Gamil Shaker - Cairo : Noha Hussein Sayed , 2018 - 132 P. : charts , facsimiles ; 25cm
Thesis (Ph.D.) - Cairo University - Faculty of Pharmacy - Department of Biochemistry
Peroxisome proliferator activated receptor gamma (PPARÞ) is a nuclear receptor that is deregulated in obesity. PPARÞ exerts diverse antineoplastic effects. Attempting to determine the clinical relevance of the epigenetic mechanisms controlling the expression PPARÞ and susceptibility to colorectal cancer (CRC) in obese subjects, this study investigated the role of some microRNAs and DNA methylation on the deregulation of PPARÞ. Seventy CRC patients (34 obese and 36 lean), 22 obese and 24 lean healthy controls were included. MicroRNA levels were measured in serum. PPARÞ promoter methylation was evaluated in blood. PPARÞ level was evaluated by measuring mRNA level in blood and protein level in serum. The tested microRNAs 27b, 130b and 138 were significantly upregulated in obese and CRC patients. Obese and CRC patients had significantly low levels of PPARÞ. A significant negative correlation was found between PPARÞ levels and the studied microRNAs. There was a significant PPARÞ promoter hypermethylation in CRC patients that correlated to low PPARÞ levels. Our results suggest that upregulation of microRNAs 27b, 130b and 138 is associated with susceptibility to CRC in obese subjects through PPARÞ downregulation. Hypermethylation of PPARÞ gene promoter is associated with CRC through suppression of PPARÞ regardless of BMI
Colorectal cancer Obesity PPARÞ