TET1-mediated DNA hypomethylation regulates the expression of MUC4 in lung cancer

Seiya Yokoyama, Michiyo Higashi, Hideaki Tsutsumida, Jouji Wakimoto, Tomofumi Hamada, Edwin Wiest, Kei Matsuo, Ikumi Kitazono, Yuko Goto, Xin Guo, Taiji Hamada, Sohsuke Yamada, Tsubasa Hiraki, Suguru Yonezawa, Surinder K. Batra, Michael A. Hollingsworth, Akihide Tanimoto

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


Lung cancer remains a disease of high mortality, despite advanced diagnostic techniques. Mucins (MUC) play crucial roles in carcinogenesis and tumor invasion in lung neoplasms. Our immunohistochemistry (IHC) studies have shown that high MUC4 expression correlates with a poor outcome. We have also shown that the expression of several mucin genes in cancer cell lines is regulated by DNA methylation. We evaluated the expression level of MUC4, mRNA and several DNA hypomethylation factors in lung tissue samples from 33 patients with various lung lesions. The results indicated that the DNA methylation status of MUC4 matched the expression level of mRNA. In addition, the TET1 (Ten-Eleven Translocation) mRNA showed a significant correlation with the status of DNA methylation of MUC4. Furthermore, the treatment of a lung cancer cell line with TET1 siRNA caused a reduction in MUC4 mRNA expression. Thus, we suggest that TET1 mediated DNA hypomethylation plays a key role in the expression of MUC4. This is the first report that TET1 mediated DNA hypomethylation regulates the expression of MUC4 in lung cancer. The analysis of these epigenetic changes may be useful for diagnosing carcinogenic risk.

Original languageEnglish (US)
Pages (from-to)517-527
Number of pages11
JournalGenes and Cancer
Issue number3-4
StatePublished - Mar 2017


  • DNA methylation
  • Lung cancer
  • MUC4
  • Pathology
  • Risk factor

ASJC Scopus subject areas

  • Genetics
  • Cancer Research


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