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Ten-eleven translocation 1 dysfunction reduces 5-hydroxymethylcytosine expression levels in gastric cancer cells

Kuo-Chiang Wang1, Chi-Hsiang Kang1, Chung-Yu Tsai1

  • 1Division of General Surgery, Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan, R.O.C.

Oncology Letters
|December 30, 2017
PubMed

Insights

Gastric cancer cells show reduced 5-hydroxymethylcytosine (5hmC) levels, linked to ten-eleven translocation (TET1) protein dysfunction. TET1 mislocalization and decreased expression contribute to 5hmC depletion, potentially driving gastric cancer progression.

Area of Science:

  • Epigenetics
  • Cancer Biology
  • Molecular Oncology

Background:

  • 5-hydroxymethylcytosine (5hmC) is a crucial epigenetic mark derived from 5-methylcytosine (5mC).
  • Expression of 5hmC is often reduced in various cancers, including gastric cancer, but the underlying mechanisms are not fully understood.
  • The ten-eleven translocation (TET) protein family catalyzes 5hmC formation.

Purpose of the Study:

  • To investigate the expression levels of 5hmC, 5-methylcytosine (5mC), TET1, and TET2 in gastric cancer tissues.
  • To elucidate the relationship between 5hmC depletion and TET protein expression and localization in gastric cancer.
  • To explore the role of TET1 dysfunction in gastric cancer progression.

Main Methods:

  • Immunohistochemistry was employed to assess the expression and subcellular localization of 5mC, 5hmC, TET1, and TET2 in gastric cancer tissues and adjacent normal tissues.

Main Results:

  • Gastric cancer tissues exhibited significantly lower 5hmC expression levels compared to normal tissues.
  • Reduced 5hmC levels were correlated with decreased TET1 protein expression.
  • TET1 protein mislocalization was significantly associated with diminished 5hmC expression in gastric cancer cells.
  • Ectopic expression of TET1 may restore 5hmC levels in gastric cancer cells.

Conclusions:

  • TET1 dysfunction, including decreased expression and aberrant subcellular localization, leads to reduced 5hmC levels in gastric cancer.
  • The depletion of 5hmC due to TET1 dysfunction is implicated as a significant factor in the progression of gastric cancer.
Keywords:
DNA methylationdemethylationgastric cancerhydroxylmethylation

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