RASSF1A Site-Specific Methylation Hotspots in Cancer and Correlation with RASSF1C and MOAP-1.
Epigenetic silencing of RASSF1A is frequently observed in numerous cancers and has been previously reported. The promoter region of RASSF1A is predicted to have 75 CpG sites, and very few studies demonstrate how the methylation of these sites affects expression. In addition, the expression relationship between RASSF1A and its downstream target, modulator of apoptosis 1 (MOAP-1), is poorly understood. In this study, we have explored the mRNA expression of RASSF1A, MOAP-1 and the well-characterized splice variant of RASSF1, RASSF1C, in cancer cell lines and primary tumors. We confirmed that the RASSF1A promoter is robustly methylated within a 32-CpG region in solid tumors and results in lower mRNA expression. The MOAP-1 promoter contains ~110 CpG sites, but was not found to be methylated in cancer cell lines when 19 predicted CpG sites were explored. Interestingly, MOAP-1 mRNA expression positively correlated with RASSF1A expression in numerous cancers, whereas RASSF1C expression remained the same or was increased in cell lines or tissues with epigenetic loss of RASSF1A. We speculate that MOAP-1 and RASSF1A may be more intimately connected than originally thought, and the expression of both are warranted in experimental designs exploring the biology of the RASSF1A/MOAP-1 molecular pathway.
Department of Pediatrics, Faculty of Medicine and Dentistry, University of Alberta, 113 Street 87 Avenue, Edmonton, AB T6G 2E1, Canada. volodko@ualberta.ca.
Natalia
N
Volodko
Department of Biochemistry, Faculty of Medicine and Dentistry, University of Alberta, 113 Street 87 Avenue, Edmonton, AB T6G 2E1, Canada. salla@ualberta.ca.
Mohamed
M
Salla
Department of Pediatrics, Faculty of Medicine and Dentistry, University of Alberta, 113 Street 87 Avenue, Edmonton, AB T6G 2E1, Canada. zare@ualberta.ca.
Alaa
A
Zare
Department of Pediatrics, Faculty of Medicine and Dentistry, University of Alberta, 113 Street 87 Avenue, Edmonton, AB T6G 2E1, Canada. abulghas@ualberta.ca.
El-Arbi
el-A
Abulghasem
Department of Experimental Oncology, Faculty of Medicine and Dentistry, University of Alberta, 113 Street 87 Avenue, Edmonton, AB T6G 2E1, Canada. kvincent@ualberta.ca.
Krista
K
Vincent
Department of Biochemistry, Faculty of Medicine and Dentistry, University of Alberta, 113 Street 87 Avenue, Edmonton, AB T6G 2E1, Canada. benesch@ualberta.ca.
Matthew G K
MG
Benesch
Department of Surgical Oncology, Faculty of Medicine and Dentistry, University of Alberta, 113 Street 87 Avenue, Edmonton, AB T6G 2E1, Canada. todd.mcmullen@ualberta.ca.
Todd P W
TP
McMullen
Departments of Surgery, University of Calgary, 1331-29<sup>th</sup> St NW, Calgary, AB T2N 4N2, Canada. oliver.bathe@albertahealthservices.ca.|Tom Baker Cancer Centre, Department of Oncology, University of Calgary, 1331-29<sup>th</sup> St NW, Calgary, AB T2N 4N2, Canada. oliver.bathe@albertahealthservices.ca.
Oliver F
OF
Bathe
Department of Experimental Oncology, Faculty of Medicine and Dentistry, University of Alberta, 113 Street 87 Avenue, Edmonton, AB T6G 2E1, Canada. postovit@ualberta.ca.
Lynne
L
Postovit
Department of Pediatrics, Faculty of Medicine and Dentistry, University of Alberta, 113 Street 87 Avenue, Edmonton, AB T6G 2E1, Canada. sbaksh@ualberta.ca.|Department of Biochemistry, Faculty of Medicine and Dentistry, University of Alberta, 113 Street 87 Avenue, Edmonton, AB T6G 2E1, Canada. sbaksh@ualberta.ca.|Department of Experimental Oncology, Faculty of Medicine and Dentistry, University of Alberta, 113 Street 87 Avenue, Edmonton, AB T6G 2E1, Canada. sbaksh@ualberta.ca.|Heritage Medical Research Center, Cancer Research Institute of Northern Alberta, University of Alberta, Edmonton, AB T6G 2R7, Canada. sbaksh@ualberta.ca.|Women and Children's Health Research Institute, Edmonton Clinic Health Academy (ECHA), University of Alberta, 4-081 11405 87 Avenue NW Edmonton, AB T6G 1C9, Canada. sbaksh@ualberta.ca.
Shairaz
S
Baksh
DNMT; MOAP-1; RASSF1A; RASSF1C; cancer; epigenetics