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Alcohol induces cell proliferation via hypermethylation of ADHFE1 in colorectal cancer cells

  • Ji W. Moon
  • , Soo K. Lee
  • , Yong W. Lee
  • , Jung O. Lee
  • , Nami Kim
  • , Hye J. Lee
  • , Jung S. Seo
  • , Jin Kim
  • , Hyeon S. Kim
  • , Sun Hwa Park*
  • *Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Background: The hypermethylation of Alcohol dehydrogenase iron containing 1 (ADHFE1) was recently reported to be associated with colorectal cancer (CRC) differentiation. However, the effect of alcohol on ADHFE1 hypermethylation in CRC is still unclear.Methods: The methylation status and expression levels of ADHFE1 were investigated in primary tumor tissues and adjacent normal tissues of 73 patients with CRC, one normal colon cell line, and 4 CRC cell lines (HT-29, SW480, DLD-1, and LoVo) by quantitative methylation-specific polymerase chain reaction (QMSP) and real-time reverse transcription polymerase chain reaction (real time PCR), respectively. The effect of alcohol on the methylation status of ADHFE1 was analyzed in HT-29, SW480, DLD-1, and CCD18Co cells using QMSP, real-time PCR, immunoblot, and cell proliferation assay.Results: ADHFE1 was hypermethylated in 69 of 73 CRC tissues (95%) compared to adjacent normal tissues (p < 0.05). The mRNA expression of ADHFE1 was significantly reduced in CRC compared to adjacent normal tissues (p < 0.05) and its expression was decreased in the alcohol consumption group (p < 0.05). ADHFE1 was hypermethylated and its expression was decreased in 4 CRC cell lines compared with normal colon cell line. Alcohol induced hypermethylation of ADHFE1, decreased its expression, and stimulated cell proliferation of HT-29, SW480, and DLD-1cells.Conclusion: These results demonstrate that the promoter hypermethylation of ADHFE1 is frequently present in CRC and alcohol induces methylation-mediated down expression of ADHFE1 and proliferation of CRC cells.

Original languageEnglish
Article number377
JournalBMC Cancer
Volume14
Issue number1
DOIs
Publication statusPublished - 2014 May 28

Bibliographical note

Funding Information:
This study was supported by a Korea University Grant (K1132261) and the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (grant number: 2010–0024117).

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

  1. SDG 3 - Good Health and Well-being
    SDG 3 Good Health and Well-being

Keywords

  • ADHFE1
  • Alcohol
  • Colorectal cancer
  • Hypermethylation
  • Quantitative methylation-specific polymerase chain reaction

ASJC Scopus subject areas

  • Oncology
  • Genetics
  • Cancer Research

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