Hypermethylation and Post-Transcriptional Regulation of DNA Methyltransferases in the Ovarian Carcinomas of the Laying Hen

Jin Young Lee, Wooyoung Jeong, Whasun Lim, Chul Hong Lim, Seung Min Bae, Jinyoung Kim, Fuller W. Bazer, Gwonhwa Song

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

DNA methyltransferases (DNMTs) are key regulators of DNA methylation and have crucial roles in carcinogenesis, embryogenesis and epigenetic modification. In general, DNMT1 has enzymatic activity affecting maintenance of DNA methylation, whereas DNMT3A and DNMT3B are involved in de novo methylation events. Although DNMT genes are well known in mammals including humans and mice, they are not well studied in avian species, especially the laying hen which is recognized as an excellent animal model for research on human ovarian carcinogenesis. Results of the present study demonstrated that expression of DNMT1, DNMT3A and DNMT3B genes was significantly increased, particularly in the glandular epithelia (GE) of cancerous ovaries, but not normal ovaries. Consistent with this result, immunoreactive 5-methylcytosine protein was predominantly abundant in nuclei of stromal and GE cells of cancerous ovaries, but it was also found that, to a lesser extent, in nuclei of stromal cells of normal ovaries. Methylation-specific PCR analysis detected hypermethylation of the promoter regions of the tumor suppressor genes in the initiation and development of chicken ovarian cancer. Further, several microRNAs, specifically miR-1741, miR-16c, and miR-222, and miR-1632 were discovered to influence expression of DNMT3A and DNMT3B, respectively, via their 3′-UTR which suggests post-transcriptional regulation of their expression in laying hens. Collectively, results of the present study demonstrated increased expression of DNMT genes in cancerous ovaries of laying hens and post-transcriptional regulation of those genes by specific microRNAs, as well as control of hypermethylation of the promoters of tumor suppressor genes.

Original languageEnglish
Article numbere61658
JournalPloS one
Volume8
Issue number4
DOIs
Publication statusPublished - 2013 Apr 17

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Fingerprint Dive into the research topics of 'Hypermethylation and Post-Transcriptional Regulation of DNA Methyltransferases in the Ovarian Carcinomas of the Laying Hen'. Together they form a unique fingerprint.

  • Cite this