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The effect of high glucose levels on the hypermethylation of protein phosphatase 1 regulatory subunit 3C (PPP1R3C) gene in colorectal cancer

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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.

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Acknowledgements

This study was supported by the Basic Science Research Programme through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (grant number: 2010-0024117).

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Authors and Affiliations

  1. Department of Anatomy, Korea University Anam Hospital, Korea University College of Medicine, 126-1, Anam-dong 5-ga, Seongbuk-gu, Seoul, South Korea

    SOO KYUNG LEE, JI WOOK MOON, YONG WOO LEE, JUNG OK LEE, SU JIN KIM, NAMI KIM, HYEON SOO KIM & SUN-HWA PARK

  2. Department of General Surgery, Korea University Anam Hospital, Korea University College of Medicine, 126-1, Anam-dong 5-ga, Seongbuk-gu, Seoul, South Korea

    JIN KIM

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  1. SOO KYUNG LEE
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  2. JI WOOK MOON
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  3. YONG WOO LEE
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  4. JUNG OK LEE
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  5. SU JIN KIM
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  9. SUN-HWA PARK
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Correspondence to SUN-HWA PARK.

Additional information

[Lee S. K., Moon J. W., Lee Y. W., Lee J. O., Kim S. J., Kim N., Kim J., Kim H. S. and Park S.-H. 2015 The effect of high glucose levels on the hypermethylation of protein phosphatase 1 regulatory subunit 3C (PPP1R3C) gene in colorectal cancer. J. Genet. 94, xx–xx]

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LEE, S.K., MOON, J.W., LEE, Y.W. et al. The effect of high glucose levels on the hypermethylation of protein phosphatase 1 regulatory subunit 3C (PPP1R3C) gene in colorectal cancer. J Genet 94, 75–85 (2015). https://doi.org/10.1007/s12041-015-0492-2

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  • DOI: https://doi.org/10.1007/s12041-015-0492-2

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