The Differential DNA Hypermethylation Patterns of microRNA-137 and microRNA-342 Locus in Early Colorectal Lesions and Tumours

Biomolecules. 2019 Sep 21;9(10):519. doi: 10.3390/biom9100519.

Abstract

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.

Keywords: colorectal cancer; methylation; miRNA-137; miRNA-342; microRNA; precursor colon/rectum polyps.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Biomarkers, Tumor / genetics
  • Colorectal Neoplasms / diagnosis
  • Colorectal Neoplasms / genetics*
  • CpG Islands
  • DNA Methylation*
  • Epigenesis, Genetic
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • Prognosis
  • Promoter Regions, Genetic
  • Sex Factors
  • Young Adult

Substances

  • Biomarkers, Tumor
  • MIRN137 microRNA, human
  • MIRN342 microRNA, human
  • MicroRNAs