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

  • Suphakit Khowutthitham
  • Chumpol Ngamphiw
  • Wachiraporn Wanichnopparat
  • Kulachanya Suwanwongse
  • Sissades Tongsima
  • Chatchawit Aporntewan
  • Apiwat Mutirangura
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
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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)
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13258_2012_58_MOESM2_ESM.pdf (123 kb)
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13258_2012_58_MOESM4_ESM.pdf (350 kb)
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Copyright information

© The Genetics Society of Korea and Springer Netherlands 2012

Authors and Affiliations

  • Suphakit Khowutthitham
    • 1
  • Chumpol Ngamphiw
    • 1
    • 2
  • Wachiraporn Wanichnopparat
    • 3
  • Kulachanya Suwanwongse
    • 3
  • Sissades Tongsima
    • 2
    • 6
  • Chatchawit Aporntewan
    • 4
    • 6
  • Apiwat Mutirangura
    • 5
    • 6
  1. 1.Inter-Department Program of Biomedical Sciences, Faculty of Graduate SchoolChulalongkorn UniversityBangkokThailand
  2. 2.Genome InstituteNational Center for Genetic Engineering and BiotechnologyKlong Luang, Pathum ThaniThailand
  3. 3.Faculty of MedicineChulalongkorn UniversityBangkokThailand
  4. 4.Department of Mathematics and Computer Science, Faculty of ScienceChulalongkorn UniversityRama IV, BangkokThailand
  5. 5.Department of Anatomy, Faculty of MedicineChulalongkorn UniversityBangkokThailand
  6. 6.Center of Excellence in Molecular Genetics of Cancer and Human DiseasesChulalongkorn UniversityBangkokThailand