PLoS One. 2015 Jun 3;10(6):e0126868. doi: 10.1371/journal.pone.0126868. eCollection 2015.

Expression and new exon mutations of the human Beta defensins and their association on colon cancer development.

Semlali A¹, Al Amri A¹, Azzi A², Al Shahrani O¹, Arafah M³, Kohailan M¹, Aljebreen AM⁴, Alharbi O⁴, Almadi MA⁵, Azzam NA⁴, Parine NR¹, Rouabhia M⁶, Alanazi MS¹.

Author information

1: Genome Research Chair, Department of Biochemistry, College of Science King Saud University, Riyadh, Kingdom of Saudi Arabia.
2: College of Medicine, Al Imam Muhammad Ibn Saud Islamic University (IMSIU), Riyadh, Kingdom of Saudi Arabia.
3: College of Medicine, King Saud University, Riyadh, Kingdom of Saudi Arabia.
4: College of Medicine, King Saud University, Riyadh, Kingdom of Saudi Arabia; Division of Gastroenterology, King Khalid University Hospital, King Saud University, Riyadh, Saudi Arabia.
5: Division of Gastroenterology, King Khalid University Hospital, King Saud University, Riyadh, Saudi Arabia; Division of Gastroenterology, The McGill University Health Center, Montreal General Hospital, McGill University, Montreal, Canada.
6: Groupe de Recherche en Écologie Buccale, Département de stomatologie, Faculté de Médecine Dentaire, Université Laval, Québec, Québec, Canada.

Abstract

The development of cancer involves genetic predisposition and a variety of environmental exposures. Genome-wide linkage analyses provide evidence for the significant linkage of many diseases to susceptibility loci on chromosome 8p23, the location of the human defensin gene cluster. Human β-defensins (hBDs) are important molecules of innate immunity. This study was designed to analyze the expression and genetic variations in hBDs (hBD-1, hBD-2, hBD-3 and hBD-4) and their putative association with colon cancer. hBD gene expression and relative protein expression were evaluated by Real-Time polymerase chain reaction (qPCR) and immunohistochemistry, respectively, from 40 normal patients and 40 age-matched patients with colon cancer in Saudi Arabia. In addition, hBD polymorphisms were genotyped by exon sequencing and by promoter methylation. hBD-1, hBD-2, hBD-3 and hBD-4 basal messenger RNA expression was significantly lower in tumor tissues compared with normal tissues. Several insertion mutations were detected in different exons of the analyzed hBDs. However, no methylation in any hBDs promoters was detected because of the limited number of CpG islands in these regions. We demonstrated for the first time a link between hBD expression and colon cancer. This suggests that there is a significant link between innate immunity deregulation through disruption of cationic peptides (hBDs) and the potential development of colon cancer.