Downregulation and DNA methylation of ECRG4 in gastric cancer

Abstract

BackgroundEsophageal cancer-related gene 4 (ECRG4) is a novel candidate tumor suppressor gene. Our study investigated the expression and function of ECRG4 in gastric cancer and highlighted the role of DNA hypermethylation at the promoter in silencing the ECRG4 expression.MethodsThe GSE63089 data set was obtained from the Gene Expression Omnibus and analyzed for differentially expressed genes. Carcinoma and para-carcinoma tissues of 102 patients with gastric cancer were collected from January 2010 to July 2011. Immunohistochemistry, real-time polymerase chain reaction (PCR), and western blot analyses were performed to evaluate the expression of ECRG4. After measuring the change in the level of ECRG4 expression, CCK-8, Transwell, and flow cytometric cell cycle assays were performed. In addition, methylation-specific PCR was performed to detect the methylation state of ECRG4, and 5-aza-2′-deoxycytidine was used for demethylation of ECRG4. All statistical analyses were performed using the SPSS 17.0 software.ResultsWe found that ECRG4 expression was downregulated in gastric cancer, and this was closely related to lymph node metastasis. After ECRG4 was silenced using a specific small interfering RNA, the BGC-823 cell line became highly aggressive and proliferative. In addition, we verified whether downregulation of ECRG4 was highly correlated with DNA methylation of the ECRG4 promoter and found that the demethylating agent 5-aza-2′-deoxycytidine could effectively enhance ECRG4 expression.ConclusionThe aberrant expression of ECRG4 is associated with hypermethylation in the promoter region and plays an important role in the malignancy of gastric cancer. Therefore, ECRG4 may be a potential biomarker for molecular diagnosis of gastric cancer, and the use of 5-Aza-dC to reverse the hypermethylation of ECRG4 may be a new approach to the treatment of gastric cancer.

ECRG4 Represses Cell Proliferation and Invasiveness via NFIC/OGN/NF-κB Signaling Pathway in Bladder Cancer

“…A study has reported that ECRG4 is downregulated and acts as a tumor suppressor gene in most types of cancers (Qin and Zhang, 2019). Several studies have shown that the ECRG4 promoter is frequently hypermethylated in patients with breast cancer, gastric cancer, and nasopharyngeal carcinoma, resulting in the downregulation of ECRG4 (You et al, 2015;Deng et al, 2018;Tang et al, 2019). Consistent with a previous study that reported that ECRG4 is hypermethylated in BCa cells (Rose et al, 2020), our results further demonstrated that ECRG4 is significantly downregulated in BCa tissues and cell lines.…”

“…Esophageal cancer-related gene-4 (ECRG4 or C2orf40) has been characterized as a tumor suppressor gene in several types of cancers, such as colorectal cancer ( Gotze et al, 2009 ; Cai et al, 2016 ), esophageal squamous cell carcinoma (ESCC; Mori et al, 2007 ; Li et al, 2011 ; Wen and Hu, 2015 ), breast cancer ( Sabatier et al, 2011 ; Lu et al, 2013 ; You et al, 2016 ; Tang et al, 2019 ), renal cell carcinoma ( Luo et al, 2016 ), gastric cancer ( Deng et al, 2018 ), and nasopharyngeal carcinoma ( Chen J.Y. et al, 2017 ).…”

UNC5A, an epigenetically silenced gene, functions as a tumor suppressor in non-small cell lung cancer

“…We found a CpG island was located in the prmoter region of UNC5A, implying the possibility of epigenetic regulation of UNC5A. The expression of epigenetically silenced gene could be recovered by demethylation agent 5-Aza ( Deng et al, 2018 , Karakoula et al, 2014 , Yamamura et al, 2013 ). Thus, we measured UNC5A expression in NSCLC cells cultured in the presence of 5-Aza.…”

Identification Hub Genes of Consensus Molecular Subtype Correlation With Immune Infiltration and Predict Prognosis in Gastric Cancer

“…C2orf40 encodes a protein called esophageal cancer-related gene-4 (ECRG4), which is down-regulated by hypermethylation of its promoter in diverse types of tumors, including hepatocellular carcinoma [33], gastric cancer [34]，breast cancer [35].…”