DNA methylation and histone H3-K9 modifications contribute to MUC17 expression

Sho Kitamoto, Norishige Yamada, Seiya Yokoyama, Izumi Houjou, Michiyo Higashi, Masamichi Goto, Surinder K. Batra, Suguru Yonezawa

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

MUC17 glycoprotein is a membrane-associated mucin that is mainly expressed in the digestive tract. It has been suggested that MUC17 expression is correlated with the malignancy potential of pancreatic ductal adenocarcinomas (PDACs). In the present study, we provided the first report of the MUC17 gene expression through epigenetic regulation such as promoter methylation, histone modification and microRNA (miRNA) expression. Near the transcriptional start site, the DNA methylation level of MUC17-negative cancer cell lines (e.g. PANC1) was high, whereas that of MUC17-positive cells (e.g. AsPC-1) was low. Histone H3-K9 (H3-K9) modification status was also closely related to MUC17 expression. Our results indicate that DNA methylation and histone H3-K9 modification in the 5' flanking region play a critical role in MUC17 expression. Furthermore, the hypomethylation status was observed in patients with PDAC. This indicates that the hypomethylation status in the MUC17 promoter could be a novel epigenetic marker for the diagnosis of PDAC. In addition, the result of miRNA microarray analysis showed that five potential miRNA candidates existed. It is also possible that the MUC17 might be post-transcriptionally regulated by miRNA targeting to the 3'-untranslated region of its mRNA. These understandings of the epigenetic changes of MUC17 may be of importance for the diagnosis of carcinogenic risk and the prediction of outcomes for cancer patients.

Original languageEnglish (US)
Pages (from-to)247-256
Number of pages10
JournalGlycobiology
Volume21
Issue number2
DOIs
StatePublished - Feb 2011

Keywords

  • DNA methylation
  • Epigenetics
  • MUC17
  • Mucin
  • Pancreatic cancer

ASJC Scopus subject areas

  • Biochemistry

Fingerprint Dive into the research topics of 'DNA methylation and histone H3-K9 modifications contribute to MUC17 expression'. Together they form a unique fingerprint.

Cite this