Journal of Cancer Prevention 2014; 19(4): 259-264
Published online December 31, 2014
© Korean Society of Cancer Prevention
Hye-Kyung Na, and Jeong-Hwa Woo
Department of Food and Nutrition, College of Human Ecology, Sungshin Women’s University, Seoul, Korea
Correspondence to :
Hye-Kyung Na, Department of Food and Nutrition, College of Human Ecology, Sungshin Women’s University, 55 Dobong-ro 76ga-gil, Gangbuk-gu, Seoul 142-732, Korea, Tel: +82-2-920-7688, Fax: +82-2-920-2076, E-mail: firstname.lastname@example.org
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Gastric cancer is one of the most common malignancies in the world.1 Although the incidence of gastric cancer is declining, its prognosis remains poor. The etiology of gastric cancer is multifactorial which includes Epstein Barr virus,
Aberrant DNA methylation is one of the most prevalent epigenetic changes, which usually takes place at the 5’position of the cytosine ring within CpG dinucleotides, and its consequence is the silencing of genes and noncoding genomic regions. The modification at 5-methyl cytosine is catalyzed by a group of enzymes termed DNA methyltransferases (DNMTs).8 There are three main isoforms of DNMTs: DNMT1, which maintains the existing methylation patterns following DNA replication, DNMT3A, and DNMT3B that target unmethylated CpGs to initiate methylation.9 Overexpression of DNMT1, DNMT3A, and DNMT3B was observed in gastric cancer tissues.10 Moreover, co-expression of DNMT1 and DNMT3A was significantly associated with lymph node metastasis. It has been reported that the genetic variations in the DNMT3A1 promoter contribute to the susceptibility to gastric cancer.11
Approximately 400 genes that are actively expressed in normal gastric epithelial cells are estimated to be inactivated in gastric cancers as a result of hypermethylation of the CpG island present in their promoters.12 Methylation in tumor suppressor genes and those encoding molecules involved in regulating cell cycle, cell adherent/invasion/migration, cell growth, apoptosis, etc., is one of the most well-defined epigenetic alterations implicated in gastric carcinogenesis.13 Aberrant CpG island hypermethylation occurs early in the multi-stage gastric carcinogenesis and tends to increase with the step-wise progression of the malignancy.14 Therefore, any insightful understanding of aberrant methylation and subsequent gene silencing is essential for cancer prediction, prevention, treatment, and prognosis.
Chronic inflammation is a well known factor responsible for promotion of many cancers. Approximately 15% to 20% of all human malignancies are related to chronic inflammation.29 Gastric cancer is a typical inflammation-associated malignancy, being closely linked to
Generation of NO by iNOS induction is a common strategy exploited by the host to fight
One of the mechanisms underlying
Glutathione peroxidase 3 (GPX3) catalyzes the inactivation/neutralization of hydrogen peroxide and lipid peroxides by reduced GSH. Down-regulation or silencing of GPX3 via promoter hypermethylation was observed in some gastric cancer cell lines and gastric cancers specimens, as compared to adjacent normal gastric tissues.42 In addition, loss of GPX1 expression and its promoter methylation were closely associated with advanced gastric cancer development and lymphatic invasion.42,43 These findings suggest that there is a vicious cycle between ROS and low levels of antioxidant enzymes. Down-regulation of antioxidant enzymes enhances the generation of ROS and subsequently triggers aberrant methylation of CpG islands located in the promoter regions of antioxidant enzymes (Fig. 1).
Nuclear factor-erythroid 2-related factor 2 gene (Nrf2), a master regulator of many critical anti-oxidative stress defense genes, has been known to be inactivated through promoter CpG methylation/histone modifications.44 Heat shock protein B reduced Nrf2 gene accumulation and expression of superoxide dismutase, heme oxygenase-1, and NAD(P)H:quinone oxidoreductase- 1 via upregulation of Keap1 expression.45 In addition, promoter polymorphisms of
Recently, accumulating data suggest that some miRNA can function as oncogenes or tumor suppressors. Silencing of some miRNAs in tumors is associated with CpG island hypermethylation. 47 Sixteen miRNAs were upregulated in gastric carcinoma. These include miR-223, miR-21, miR-23b, miR-222, miR-25, miR-23a, miR-221, miR-107, miR-103, miR-99a, miR-100, miR-125b, miR-92, miR-146a, miR-214, and miR-191.48 In contrast, six miRNAs including let-7a, miR-126, miR-210, miR-181b, miR-197, and miR-30aa-5p were down-regulated in gastric carcinoma.48 Expression levels of several miRNAs, such as miR-210, miR-375 and miR-99a, were found to be reduced in the gastric epithelium of Mongolian gerbils infected with
Suhn Hyung Kim, Joo Weon Lim, Hyeyoung KimJ Cancer Prev 2019; 24(1): 54-58 https://doi.org/10.15430/JCP.2019.24.1.54
Jung Won Lee, Nayoung Kim, Ji Hyun Park, Hee Jin Kim, Hyun Chang, Jung Min Kim, Jin-Wook Kim, and Dong Ho LeeJournal of Cancer Prevention 2017; 22(1): 33-39 https://doi.org/10.15430/JCP.2017.22.1.33
Yo Han Park, and Nayoung KimJournal of Cancer Prevention 2015; 20(1): 25-40 https://doi.org/10.15430/JCP.2015.20.1.25