title: The effect of high glucose levels on the hypermethylation of protein phosphatase 1 regulatory subunit 3C (PPP1R3C) gene in colorectal cancer.
abstract: DNA methylation is an epigenetic event that occurs frequently in colorectal cancer (CRC). Increased glucose level is a strong risk factor for CRC. Protein phosphatase 1 regulatory subunit 3C (PPP1R3C) modulates glycogen metabolism, particularly glycogen synthesis. The aim of this study was to investigate the effect of high glucose levels on DNA methylation of PPP1R3C in CRC. PPP1R3C was significantly hypermethylated in CRC tissues (76/105, 72.38%, P <0.05) and colon cancer cell lines (P < 0.05). CRC tissues obtained from patients with high glucose levels showed that the methylation of PPP1R3C was lower than in patients who had normal levels of glucose. When DLD-1 cells were cultured under conditions of high glucose, the methylation of PPP1R3C was repressed. The expression of PPP1R3C was inversely related to methylation status. In addition, a promoter luciferase assay showed that the transcriptional activity of PPP1R3C was increased in high glucose culture conditions. The number of cells decreased when PPP1R3C was silenced in DLD-1 cells. These results suggest that PPP1R3C, a novel hypermethylated gene in CRC, may play a critical role in cancer cell growth in association with glucose levels.
authors.affiliation: Department of Anatomy, Korea University Anam Hospital, Korea University College of Medicine, 126-1, Anam-dong 5-ga, Seongbuk-gu, Seoul, South Korea. parksh@korea.ac.kr.
authors.forename: Soo Kyung
authors.initials: SK
authors.lastname: Lee
authors.forename: Ji Wook
authors.initials: JW
authors.lastname: Moon
authors.forename: Yong Woo
authors.initials: YW
authors.lastname: Lee
authors.forename: Jung Ok
authors.initials: JO
authors.lastname: Lee
authors.forename: Su Jin
authors.initials: SJ
authors.lastname: Kim
authors.forename: Nami
authors.initials: N
authors.lastname: Kim
authors.forename: Jin
authors.initials: J
authors.lastname: Kim
authors.forename: Hyeon Soo
authors.initials: HS
authors.lastname: Kim
authors.forename: Sun-Hwa
authors.initials: SH
authors.lastname: Park
mesh_terms: D000368:Aged; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000201:enzymology / Q000235:genetics*; D019175:DNA Methylation; D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology / Q000235:genetics; D044127:Epigenesis, Genetic; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005947:Glucose / Q000502:physiology*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010749:Phosphoprotein Phosphatases / Q000235:genetics* / Q000378:metabolism; D017422:Sequence Analysis, DNA
chemical_list: D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; C491294:PPP1R3C protein, human; D010749:Phosphoprotein Phosphatases; D005947:Glucose
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