title: Isocitrate Dehydrogenase 2 Dysfunction Contributes to 5-hydroxymethylcytosine Depletion in Gastric Cancer Cells.
abstract: The isocitrate dehydrogenase (IDH) family of enzymes comprises of the key functional metabolic enzymes in the Krebs cycle that catalyze the conversion of isocitrate to α-ketoglutarate (α-KG). α-KG acts as a cofactor in the conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC). However, the relationship between 5hmC and IDH in gastric cancer remains unclear. Our study revealed that the 5hmC level was substantially lower and 5mC level was slightly higher in gastric cancer tissues; however, 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC) levels did not change significantly in these tissues. We further examined the expression levels of IDH1 and IDH2 in gastric cancer tissues and observed that IDH2 levels were significantly lower in gastric cancer tissues than in the adjacent normal tissues. The ectopic expression of IDH2 can increase 5hmC levels in gastric cancer cells. In conclusion, our results suggested that IDH2 dysfunction is involved in 5hmC depletion during gastric cancer progression.
authors.affiliation: Division of General Surgery, Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, R.O.C.
authors.forename: Nan-Hua
authors.initials: NH
authors.lastname: Chou
authors.affiliation: Division of General Surgery, Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, R.O.C.
authors.forename: Chung-Yu
authors.initials: CY
authors.lastname: Tsai
authors.affiliation: Departments of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, R.O.C.
authors.forename: Ya-Ting
authors.initials: YT
authors.lastname: Tu
authors.affiliation: Division of General Surgery, Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, R.O.C.
authors.forename: Kuo-Chiang
authors.initials: KC
authors.lastname: Wang
authors.affiliation: Division of General Surgery, Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, R.O.C.
authors.forename: Chi-Hsiang
authors.initials: CH
authors.lastname: Kang
authors.affiliation: Division of General Surgery, Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, R.O.C.
authors.forename: Po-Min
authors.initials: PM
authors.lastname: Chang
authors.affiliation: Departments of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, R.O.C.
authors.forename: Guan-Cheng
authors.initials: GC
authors.lastname: Li
authors.affiliation: Center for Geriatrics and Gerontology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, R.O.C.
authors.forename: Hing-Chung
authors.initials: HC
authors.lastname: Lam
authors.affiliation: Division of General Surgery, Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, R.O.C.
authors.forename: Shiuh-Inn
authors.initials: SI
authors.lastname: Liu
authors.affiliation: Departments of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, R.O.C. Department of Chemical Biology, National Pingtung University of Education, Pingtung, Taiwan, R.O.C. kwtsai@vghks.gov.tw.
authors.forename: Kuo-Wang
authors.initials: KW
authors.lastname: Tsai
mesh_terms: D044503:5-Methylcytosine / Q000378:metabolism / Q000031:analogs & derivatives; D003596:Cytosine / Q000031:analogs & derivatives / Q000302:isolation & purification / Q000378:metabolism; D019175:DNA Methylation / Q000235:genetics*; D005260:Female; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000096:biosynthesis* / Q000235:genetics; D007656:Ketoglutaric Acids / Q000378:metabolism; D008297:Male; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: C560974:5-carboxylcytosine; C560973:5-formylcytosine; D007656:Ketoglutaric Acids; C011865:5-hydroxymethylcytosine; D044503:5-Methylcytosine; D003596:Cytosine; C538784:IDH2 protein, human; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human
keywords: DNA methylation; demethylation; gastric cancer; hydroxymethylation