DNA methyltransferase 3A promotes cell proliferation by silencing CDK inhibitor p18INK4C in gastric carcinogenesis

Scientific Reports
He CuiHong Fan

Abstract

Little is known about the roles of DNA methyltransferase 3A (DNMT3A) in gastric carcinogenesis. Here, we reported that the exogenous expression of DNMT3A promoted gastric cancer (GC) cell proliferation by accelerating the G1/S transition. Subsequently, p18INK4C was identified as a downstream target of DNMT3A. The elevated expression of DNMT3A suppressed p18INK4C at least at the transcriptional level. Depletion of p18INK4C expression in GC cells induced cell cycle progression, whereas its re-expression alleviated the effect of DNMT3A overexpression on G1/S transition. Furthermore, we found that DNMT3A modulated p18INK4C by directly binding to and silencing the p18INK4C gene via promoter hypermethylation. In clinical GC tissue specimens analyzed, the level of methylation of p18INK4C detected in tumor tissues was significantly higher than that in paired non-tumor tissues. Moreover, elevated level of DNMT3A expression was associated with the differentiation of GC tissues and was negatively correlated with the p18INK4C expression level. Taken together, our results found that DNMT3A contributes to the dysregulation of the cell cycle by repressing p18INK4C in a DNA methylation-dependent manner, suggesting that DNMT3A-p18INK4C axis inv...Continue Reading

References

May 15, 1995·Genes & Development·C J Sherr, J M Roberts
Jan 1, 1994·Human Molecular Genetics·P W Laird, R Jaenisch
Apr 6, 2000·Journal of the National Cancer Institute·G TamuraS J Meltzer
Apr 5, 2002·Nature·Ina RheeBert Vogelstein
Apr 19, 2002·Biochimica Et Biophysica Acta·Sagrario OrtegaMariano Barbacid
Jun 22, 2002·The Journal of Biological Chemistry·Alexandre BlaisClaude Labrie
Jan 31, 2003·Molecular and Cellular Biology·Feng BaiYue Xiong
Aug 7, 2004·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Yu SunJi-You Li
Sep 7, 2004·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Asahiro MorishitaShigeki Kuriyama
Jan 28, 2006·World Journal of Gastroenterology : WJG·Ling Yang
Feb 16, 2006·Cell Cycle·Tamar UzielMartine F Roussel
Feb 27, 2007·Cell·Peter A Jones, Stephen B Baylin
Jul 27, 2007·IUBMB Life·Eduardo T CánepaMaría F Ogara
Dec 26, 2007·Laboratory Investigation; a Journal of Technical Methods and Pathology·Gyeong Hoon KangPeter W Laird
Feb 7, 2008·Digestive Diseases and Sciences·Wen-Jin DingYan-Shen Peng
Feb 8, 2008·APMIS : Acta Pathologica, Microbiologica, Et Immunologica Scandinavica·Tsutomu DaaShigeo Yokoyama
Mar 14, 2008·The New England Journal of Medicine·Manel Esteller
Apr 3, 2008·Cancer Research·David A SolomonTodd Waldman
Nov 1, 2008·Genes, Chromosomes & Cancer·Matthias KirschGabriele Schackert
Jul 28, 2009·Biochemical and Biophysical Research Communications·Tao DengJian Fei
Sep 16, 2009·Carcinogenesis·Shikhar SharmaPeter A Jones
Aug 19, 2010·Epigenetics : Official Journal of the DNA Methylation Society·Nikolay Popov, Jesús Gil
Feb 8, 2011·CA: a Cancer Journal for Clinicians·Ahmedin JemalDavid Forman
May 26, 2012·Cancer Cell·Daniel D De CarvalhoPeter A Jones
Mar 1, 2011·Experimental and Therapeutic Medicine·Christoph W StreyRoman A Blaheta
Jul 11, 2014·World Journal of Gastroenterology : WJG·Xue-Yuan CaoJing Jiang

❮ Previous
Next ❯

Citations

Mar 23, 2017·Toxicological Sciences : an Official Journal of the Society of Toxicology·Dongxu GaoZhenghong Zuo
Jul 19, 2017·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Quan ZhangJing Yang
Sep 13, 2018·Journal of Molecular Recognition : JMR·Mousumi Sahu, Bibekanand Mallick
Jul 23, 2019·Journal of Neurogastroenterology and Motility·Brian G Jorgensen, Seungil Ro
Mar 4, 2017·Journal of Molecular Neuroscience : MN·Giuseppina MastrototaroAlessandro Sessa
Nov 1, 2018·BMC Cancer·Leandro MagalhãesÂndrea Ribeiro-Dos-Santos
May 13, 2017·International Journal of Oncology·Xiao-Qing ZengShi-Yao Chen
Jul 4, 2021·Digestive and Liver Disease : Official Journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver·Hui SongBing Luo

❮ Previous
Next ❯

Methods Mentioned

BETA
PCR
ChIP
flow cytometry
xenograft
immunoprecipitation

Software Mentioned

Affymetrix
Modfit
GCOS1
ImageJ

Related Concepts

Related Feeds

Cell Signaling & Cancer Epigenetics (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. This feed covers the latest research on signaling and epigenetics in cell growth and cancer.

Cancer Epigenetics & Methyl-CpG (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. Here is the latest research on cancer epigenetics and methyl-CpG binding proteins including ZBTB38.

Cancer Epigenetics

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. The epigenetic changes may or may not provide advantages for the cancer cells. Here is the latest research on cancer epigenetics.

Cancer Epigenetics and Senescence (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. The epigenetic changes may be involved in regulating senescence in cancer cells. This feed captures the latest research on cancer epigenetics and senescence.

Cancer Epigenetics (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. The epigenetic changes may or may not provide advantages for the cancer cells. Here is the latest research on cancer epigenetics.

Cancer Epigenetics & Metabolism (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. The epigenetic changes may or may not provide advantages for the cancer cells. This feed focuses on the relationship between cell metabolism, epigenetics and tumor differentiation.