The Differential DNA Hypermethylation Patterns of microRNA-137 and microRNA-342 Locus in Early Colorectal Lesions and Tumours
Elham Kashani,
Mahrooyeh Hadizadeh,
Vahid Chaleshi,
Reza Mirfakhraie,
Chris Young,
Sanaz Savabkar,
Shiva Irani,
Hamid Asadzadeh Aghdaei,
Maziar Ashrafian Bonab
Affiliations
Elham Kashani
Institue of Pathology, University of Bern, 3010 Bern, Switzerland
Mahrooyeh Hadizadeh
Department of Applied Sciences, University of the West of England (UWE-Bristol), Bristol BS16 1QY, UK
Vahid Chaleshi
Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran 19839-63113, Iran
Reza Mirfakhraie
Department of Medical Genetics, Shaheed Beheshti University of Medical Sciences, Tehran 19839 69411, Iran
Chris Young
Leicester School of Allied Health Sciences, Faculty of Health and Life Sciences, De Montfort University, Leicester LE1 9BH, UK
Sanaz Savabkar
Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran 19839-63113, Iran
Shiva Irani
Department of Biology, School of Basic Sciences, Science and Research Branch, Islamic Azad University, Tehran 1477893855, Iran
Hamid Asadzadeh Aghdaei
Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran 19839-63113, Iran
Maziar Ashrafian Bonab
Department of Applied Sciences, University of the West of England (UWE-Bristol), Bristol BS16 1QY, UK
Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide, representing 13% of all cancers. The role of epigenetics in cancer diagnosis and prognosis is well established. MicroRNAs in particular influence numerous cancer associated processes including apoptosis, proliferation, differentiation, cell-cycle controls, migration/invasion and metabolism. MiRNAs-137 and 342 are exon- and intron-embedded, respectively, acting as tumour-suppressive microRNA via hypermethylation events. Levels of miRNAs 137 and 342 have been investigated here as potential prognostic markers for colorectal cancer patients. The methylation status of miRNA-137 and miRNA-342 was evaluated using methylation-specific (MSP) polymerase chain reaction (PCR) on freshly frozen tissue derived from 51 polyps, 8 tumours and 14 normal colon mucosa specimens. Methylation status of miRNA-137 and miRNA-342 was significantly higher in tumour lesions compared to normal adjacent mucosa. Surprisingly, the methylation frequency of miR-342 (76.3%) among colorectal cancer patients was significantly higher compared to miR-137 (18.6%). Furthermore, normal tissues, adjacent to the lesions (N-Cs), displayed no observable methylation for miRNA-137, whereas 27.2% of these N-Cs showed miRNA-342 hypermethylation. MiRNA-137 hypermethylation was significantly higher in male patients and miR-342 hypermethylation correlated with patient age. Methylation status of miRNA-137 and miRNA-342 has both diagnostic and prognostic value in CRC prediction and prevention.
