The Pleckstrin and Sec7 domain-containing gene as a novel epigenetic modification marker in human gastric cancer and its clinical significance Corrigendum in /10.3892/ijo.2022.5313

Zhu,Xinjiang; Liu,Jian; Xu,Xiaoyang; Zhang,Chundong; Dai,Dongqiu

doi:10.3892/ijo.2014.2736

The Pleckstrin and Sec7 domain-containing gene as a novel epigenetic modification marker in human gastric cancer and its clinical significance

Corrigendum in: /10.3892/ijo.2022.5313

Authors:
- Xinjiang Zhu
- Jian Liu
- Xiaoyang Xu
- Chundong Zhang
- Dongqiu Dai
View Affiliations

Affiliations: Department of Gastrointestinal Surgery, The Fourth Affiliated Hospital, China Medical University, Shenyang 110032, P.R. China
Published online on: October 30, 2014 https://doi.org/10.3892/ijo.2014.2736
Pages: 195-204

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The Pleckstrin and Sec7 domain-containing (PSD) gene has been recently found to participate in the progression of several types of cancer. In the present study, we identified PSD as a candidate tumor suppressor gene silenced through epigenetic modification in gastric cancer (GC). PSD mRNA expression and DNA methylation were evaluated by real-time reverse-transcriptase polymerase chain reaction (RT-PCR) and methylation-specific PCR in GC cell lines and tissue samples. Involvement of histone modification in GC cell lines was examined by chromatin immunoprecipitation assay. We also used an siRNA-mediated approach to knock down the PSD gene in SGC7901 cells, which was utilized to detect the role of PSD in GC progression, followed by analysis of cell apoptosis and invasion. PSD gene expression was reduced in all GC cell lines compared with GES1 (an immortalized normal gastric cell line). In addition, PSD expression was markedly downregulated in gastric carcinoma tissues when compared to adjacent non-tumor tissues. Our data also indicated that PSD mRNA and protein levels were associated with tumor differentiation and lymph node metastasis. Aberrant DNA methylation status and histone modification were also found in GC cell lines. Enhanced gene expression was detected when the HGC27, AGS and BGC823 GC cell lines were treated with the DNA-demethylating agent 5-aza-2'-deoxycytidine. However, treatment with trichostatin A, a histone deacetylase inhibitor, had no effect on PSD expression in any of the GC cell lines. Suppression of PSD by siRNA led to enhanced SGC7901 cell invasion. The depletion of PSD expression inhibited cell proliferation and decreased apoptosis in SGC7901 cell lines. Knockdown of the PSD expression decreased caspase-3 and -7 protein levels in SGC7901 cells. PSD gene may function as a tumor suppressor in GC suggesting a vital role for DNA methylation and histone modification in PSD silencing. PSD expression might be a useful biomarker for epigenetic-based GC early diagnosis and may lead to the identification of new targets for pharmacological intervention.

View Figures

View References

1	Jemal A, Bray F, Center MM, Ferlay J, Ward E and Forman D: Global cancer statistics. CA Cancer J Clin. 61:69–90. 2011. View Article : Google Scholar
2	Park YS, Jin MY, Kim YJ, Yook JH, Kim BS and Jang SJ: The global histone modificaton pattern correlates with cancer recurrence and overall survival in gastric adenocarcinoma. Ann Surg Oncol. 15:1968–1976. 2008. View Article : Google Scholar : PubMed/NCBI
3	Meng CF, Zhu XJ, Peng G and Dai DQ: Role of histone modifications and DNA methylation in the regulation of O⁶-methylguanine-DNA methyltransferase gene expression in human stomach cancer cells. Cancer Invest. 28:331–339. 2010. View Article : Google Scholar : PubMed/NCBI
4	Kim M, Jang HR, Kim JH, et al: Epigenetic inactivation of protein kinase D1 in gastric cancer andits role in gastric cancer cell migration and invasion. Carcinogenesis. 29:629–637. 2008. View Article : Google Scholar : PubMed/NCBI
5	Jaenisch R and Bird A: Epigenetic regulation of gene expression: how the genome integrates intrinsic and environmental signals. Nat Genet. 33:245–254. 2003. View Article : Google Scholar : PubMed/NCBI
6	Sharma S, Kelly TK and Jones PA: Epigenetics in cancer. Carcinogenesis. 31:27–36. 2010. View Article : Google Scholar
7	Nan X, Ng HH, Johnson CA, Laherty CD, Turner BM, Eisenman RN and Bird A: Transcriptional repression by the methyl-CpG-binding protein MeCP2 involves a histone deacetylase complex. Nature. 393:386–389. 1998. View Article : Google Scholar : PubMed/NCBI
8	Hendrich B and Bird A: Identification and characterization of a family of mammalian methyl-CpG binding proteins. Mol Cell Biol. 18:6538–6547. 1998.PubMed/NCBI
9	Bird A: DNA methylation patterns and epigenetic memory. Genes Dev. 16:6–21. 2002. View Article : Google Scholar
10	Tariq M, Saze H, Probst AV, Lichota J, Habu Y and Paszkowski J: Erasure of CpG methylation in arabidopsis alters patterns of histone H3 methylation in heterochromatin. Proc Natl Acad Sci USA. 100:8823–8827. 2003. View Article : Google Scholar : PubMed/NCBI
11	Espada J, Ballestar E, Fraga MF, et al: Human DNA methyltransferase 1 is required for maintenance of the histone H3 modification pattern. J Biol Chem. 279:37175–37184. 2004. View Article : Google Scholar : PubMed/NCBI
12	Meng CF, Zhu XJ, Peng G and Dai DQ: Promoter histone H3 lysine 9 di-methylation is associated with DNA methylation and aberrant expression of p16 in gastric cancer cells. Oncol Rep. 22:1221–1227. 2009.PubMed/NCBI
13	Kondo Y, Shen L, Yan PS, Huang TH and Issa JP: Chromatin immunoprecipitation microarrays for identification of genes silenced by histone H3 lysine 9 methylation. Proc Natl Acad Sci USA. 101:7398–7403. 2004. View Article : Google Scholar : PubMed/NCBI
14	Rubinek T1, Shulman M, Israeli S, et al: Epigenetic silencing of the tumor suppressor klotho in human breast cancer. Breast Cancer Res Treat. 133:649–657. 2012. View Article : Google Scholar : PubMed/NCBI
15	Gulbins E, Coggeshall KM, Brenner B, Schlottmann K, Linderkamp O and Lang F: Fas-induced apoptosis is mediated by activation of a Ras and Rac protein-regulated signaling pathway. J Biol Chem. 271:26389–26394. 1996. View Article : Google Scholar : PubMed/NCBI
16	Esteve P, Embade N, Perona R, et al: Rho-regulated signals induce apoptosis in vitro and in vivo by a p53-independent, but Bcl2 dependent pathway. Oncogene. 17:1855–1869. 1998. View Article : Google Scholar : PubMed/NCBI
17	Perletti L, Talarico D, Trecca D, Ronchetti D and Fracchiolla NS: Identification of a novel gene, PSD, adjacent to NFKB2/lyt-10, which contains Sec7 and pleckstrin-homologydomains. Genomics. 46:251–259. 1997. View Article : Google Scholar : PubMed/NCBI
18	Okada S, Suzuki K, Takaharu K, et al: Aberrant methylation of the Pleckstrin and Sec7 domain-containing gene is implicated in ulcerative colitis-associated carcinogenesis throughits inhibitory effect on apoptosis. Int J Oncol. 40:686–694. 2012.
19	Fahrner JA, Eguchi S, Herman JG and Baylin SB: Dependence of histone modifications and gene expression on DNA hypermethylation in cancer. Cancer Res. 62:7213–7218. 2002.PubMed/NCBI
20	Cameron EE, Bachman KE, Myohane S, Herman JG and Baylin SB: Synergy of demethylation and histone deacetylase inhibition in the re-expression of genes silenced in cancer. Nat Genet. 21:103–107. 1999. View Article : Google Scholar : PubMed/NCBI
21	Li LC and Dahiya R: MethPrimer: designing primers for methylation PCRs. Bioinformatics. 18:1427–1431. 2002. View Article : Google Scholar : PubMed/NCBI
22	Fuks F: DNA methylation and histone modifications: teaming up to silence genes. Curr Opin Genet Dev. 15:490–495. 2005. View Article : Google Scholar : PubMed/NCBI
23	Wu J, Wang SH, Potter D, et al: Diverse histone modifications on histone 3 lysine 9 andtheir relation to DNA methylation in specifying gene silencing. BMC Genomics. 8:1312007. View Article : Google Scholar : PubMed/NCBI
24	Liu J, Zhu X, Xu X and Dai D: DNA promoter and histone H3 methylation downregulate NGX6 in gastric cancer cells. Med Oncol. 31:8172014. View Article : Google Scholar : PubMed/NCBI
25	Kato T, Suzuki K, Okada S, et al: Aberrant methylation of PSD disturbs. Rac1-mediated immune responses governing neutrophil chemotaxis and apoptosis in ulcerative colitis-associated carcinogenesis. Int J Oncol. 40:942–950. 2012.
26	Saez R, Chan AM, Miki T and Aaronson SA: Oncogenic activation of human R-ras by point mutations analogous to those of prototype H-ras oncogenes. Oncogene. 9:2977–2982. 1994.PubMed/NCBI
27	Nishida K, Kaziro Y and Satoh T: Anti-apoptotic function of Rac in hematopoietic cells. Oncogene. 18:407–415. 1999. View Article : Google Scholar : PubMed/NCBI
28	Eom YW, Yoo MH, Woo CH, et al: Implication of the small GTPase Rac1 in the apoptosis induced by UV in Rat-2 fibroblasts. Biochem Biophys Res Commun. 285:825–829. 2001. View Article : Google Scholar : PubMed/NCBI