Genes & Genomics

, Volume 34, Issue 5, pp 517–528

Intragenic long interspersed element-1 sequences promote promoter hypermethylation in lung adenocarcinoma, multiple myeloma and prostate cancer

Authors

  • Suphakit Khowutthitham
    • Inter-Department Program of Biomedical Sciences, Faculty of Graduate SchoolChulalongkorn University
  • Chumpol Ngamphiw
    • Inter-Department Program of Biomedical Sciences, Faculty of Graduate SchoolChulalongkorn University
    • Genome InstituteNational Center for Genetic Engineering and Biotechnology
  • Wachiraporn Wanichnopparat
    • Faculty of MedicineChulalongkorn University
  • Kulachanya Suwanwongse
    • Faculty of MedicineChulalongkorn University
  • Sissades Tongsima
    • Genome InstituteNational Center for Genetic Engineering and Biotechnology
    • Center of Excellence in Molecular Genetics of Cancer and Human DiseasesChulalongkorn University
  • Chatchawit Aporntewan
    • Department of Mathematics and Computer Science, Faculty of ScienceChulalongkorn University
    • Center of Excellence in Molecular Genetics of Cancer and Human DiseasesChulalongkorn University
    • Department of Anatomy, Faculty of MedicineChulalongkorn University
    • Center of Excellence in Molecular Genetics of Cancer and Human DiseasesChulalongkorn University
Research Article

DOI: 10.1007/s13258-012-0058-0

Cite this article as:
Khowutthitham, S., Ngamphiw, C., Wanichnopparat, W. et al. Genes Genom (2012) 34: 517. doi:10.1007/s13258-012-0058-0

Abstract

In cancers, although the methylation of long interspersed element- 1 sequences (LINE-1s) and tumor suppressor gene promoters are modified in the opposite direction, LINE-1 hypomethylation and promoter hypermethylation of some loci are directly associated. During carcinogenesis, the reduction in LINE-1 methylation occurs. Intragenic LINE-1s produces antisense RNA in introns and reduces mRNA transcription levels. Several antisense RNAs have been reported to mediate methylation of the associated CpG islands. Here we compared genome-wide promoter methylation and expression profiles of LINE-1-hypomethylated malignancies, reported in the Gene Expression Omnibus database (http://www.ncbi.nlm.nih.gov/geo), including lung adenocarcinoma, multiple myeloma and prostate cancer. Then we analysed a microarray experiment if promoters of a set of genes containing LINE-1s or Alu are commonly methylated. Finally, the differences in structural characteristics of LINE-1s were compared between LINE-1 groups. Here we found that genes that contained LINE-1s were frequently repressed (p < 0.01) and possessed promoter hypermethylation (p < 1.0E-4). The expression levels of genes containing LINE-1s with promoter hypermethylation were the lowest. Finally, the genomic distributions of gene-repressing LINE-1s and promoter-hypermethylating LINE-1s were neither co-segregated nor randomly segregated. In conclusion, cancer-associated intragenic LINE-1 epigenetic change promotes promoter hypermethylation and represses gene expression. These two mechanisms are independently influenced by genomic locations but synergistically down-regulate genes.

Keywords

Antisense RNACancer epigenomicsGene promoter hypermethylationGlobal hypomethylationIntragenic LINE-1Long interspersed element-1LINE-1 hypomethylation

Supplementary material

13258_2012_58_MOESM1_ESM.pdf (61 kb)
Supplementary material, approximately 60.9 KB.
13258_2012_58_MOESM2_ESM.pdf (123 kb)
Supplementary material, approximately 122 KB.
13258_2012_58_MOESM3_ESM.pdf (834 kb)
Supplementary material, approximately 833 KB.
13258_2012_58_MOESM4_ESM.pdf (350 kb)
Supplementary material, approximately 349 KB.

Copyright information

© The Genetics Society of Korea and Springer Netherlands 2012