Up-regulation of cancer-related genes in HepG2 cells by TCDD requires PRMT i and IV

Joohyun Lee, Eun Il Lee, Daeho Kwon, Yongchul Lim, Sangnam Oh, Minyeong Oh, Eunyoung Hong

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

The 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a well-known carcinogen, however, the biological mechanism of carcinogenesis by TCDD has not been established. Recently, protein arginine methyltransferases (PRMTs) have been identified as secondary transcription co-activators and are proposed to be co-activators of aryl hydrocarbon receptors binding to xenobiotic response elements. Both PRMT1 and PRMT4 were also reported to be involved with carcinogenesis. The aim of this study was to identify cancer-related genes that are regulated by TCDD exposure and the effect of arginine methylation on TCDD toxicity by transfecting human hepatocarcinoma cells with PRMT1 and PRMT4 siRNA. By microarray analysis, 1,461 genes were up-regulated and 1,591 genes were down-regulated by TCDD exposure. Among the 16 up-regulated genes which had functions related to cancer or metastasis, 13 genes were confirmed by quantitative real time RT-PCR: ABCG2, NRP1, SOX5, BIRC3, CD109, CYP1A1, ERBB2, MTA1, FURIN, F3, PIK3R3, NPTN and NTN4. Co-inhibition of PRMT1 and PRMT4 resulted in decreased expression of eight of these genes, MTA1, ERBB2, SOX5, CD109, FURIN, NRP1, PIK3R3 and ABCG2, all of which have been reportedly involved in breast, ovary, prostate and lung cancers, and metastasis.

Original languageEnglish
Pages (from-to)111-118
Number of pages8
JournalMolecular and Cellular Toxicology
Volume6
Issue number2
DOIs
Publication statusPublished - 2010 Jun 1

Fingerprint

Protein-Arginine N-Methyltransferases
Neoplasm Genes
Hep G2 Cells
Up-Regulation
Genes
Furin
Carcinogenesis
Neoplasm Metastasis
Aryl Hydrocarbon Receptors
Cytochrome P-450 CYP1A1
Response Elements
Xenobiotics
Microarray Analysis
Methylation
Carcinogens
Ovarian Neoplasms
Small Interfering RNA
Arginine
Transcription
Microarrays

Keywords

  • Cancer
  • Metastasis
  • PRMT1
  • PRMT4
  • Protein arginine methylation
  • TCDD

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Health, Toxicology and Mutagenesis
  • Public Health, Environmental and Occupational Health
  • Pathology and Forensic Medicine

Cite this

Up-regulation of cancer-related genes in HepG2 cells by TCDD requires PRMT i and IV. / Lee, Joohyun; Lee, Eun Il; Kwon, Daeho; Lim, Yongchul; Oh, Sangnam; Oh, Minyeong; Hong, Eunyoung.

In: Molecular and Cellular Toxicology, Vol. 6, No. 2, 01.06.2010, p. 111-118.

Research output: Contribution to journalArticle

Lee, Joohyun ; Lee, Eun Il ; Kwon, Daeho ; Lim, Yongchul ; Oh, Sangnam ; Oh, Minyeong ; Hong, Eunyoung. / Up-regulation of cancer-related genes in HepG2 cells by TCDD requires PRMT i and IV. In: Molecular and Cellular Toxicology. 2010 ; Vol. 6, No. 2. pp. 111-118.
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