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

15 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
Externally publishedYes

Fingerprint

methyltransferases
Methyltransferases
laying hens
carcinoma
Ovary
Genes
Carcinoma
tumor suppressor genes
DNA
DNA methylation
microRNA
methylation
carcinogenesis
DNA Methylation
Tumor Suppressor Genes
MicroRNAs
Methylation
epithelium
genes
promoter regions

ASJC Scopus subject areas

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

Cite this

Hypermethylation and Post-Transcriptional Regulation of DNA Methyltransferases in the Ovarian Carcinomas of the Laying Hen. / Lee, Jin Young; Jeong, Wooyoung; Lim, Whasun; Lim, Chul Hong; Bae, Seung Min; Kim, Jinyoung; Bazer, Fuller W.; Song, Gwonhwa.

In: PLoS One, Vol. 8, No. 4, e61658, 17.04.2013.

Research output: Contribution to journalArticle

Lee, Jin Young ; Jeong, Wooyoung ; Lim, Whasun ; Lim, Chul Hong ; Bae, Seung Min ; Kim, Jinyoung ; Bazer, Fuller W. ; Song, Gwonhwa. / Hypermethylation and Post-Transcriptional Regulation of DNA Methyltransferases in the Ovarian Carcinomas of the Laying Hen. In: PLoS One. 2013 ; Vol. 8, No. 4.
@article{1b5eaeb283454f35b36c8b75b97dc3d7,
title = "Hypermethylation and Post-Transcriptional Regulation of DNA Methyltransferases in the Ovarian Carcinomas of the Laying Hen",
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.",
author = "Lee, {Jin Young} and Wooyoung Jeong and Whasun Lim and Lim, {Chul Hong} and Bae, {Seung Min} and Jinyoung Kim and Bazer, {Fuller W.} and Gwonhwa Song",
year = "2013",
month = "4",
day = "17",
doi = "10.1371/journal.pone.0061658",
language = "English",
volume = "8",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "4",

}

TY - JOUR

T1 - Hypermethylation and Post-Transcriptional Regulation of DNA Methyltransferases in the Ovarian Carcinomas of the Laying Hen

AU - Lee, Jin Young

AU - Jeong, Wooyoung

AU - Lim, Whasun

AU - Lim, Chul Hong

AU - Bae, Seung Min

AU - Kim, Jinyoung

AU - Bazer, Fuller W.

AU - Song, Gwonhwa

PY - 2013/4/17

Y1 - 2013/4/17

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84876270654&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84876270654&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0061658

DO - 10.1371/journal.pone.0061658

M3 - Article

VL - 8

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 4

M1 - e61658

ER -