DNMT family induces down-regulation of NDRG1 via DNA methylation and clinicopathological significance in gastric cancer

Abstract

Background Aberrant DNA methylation of tumor suppressor genes is a common event in the development and progression of gastric cancer (GC). Our previous study showed NDRG1, which could suppress cell invasion and migration, was frequently down-regulated by DNA methylation of its promoter in GC. Purpose and Methods To analyze the relationship between the expression and DNA methylation of NDRG1 and DNA methyltransferase (DNMT) family. We performed a comprehensive comparison analysis using 407 patients including sequencing analysis data of GC from TCGA. Results NDRG1 was down-regulated in GC, and was negatively correlative to DNMT1 (r = −0.11, p = 0.03), DNMT3A (r = −0.10, p = 0.01), DNMT3B (r = −0.01, p = 0.88), respectively, whereas the DNA methylation of NDRG1 was positively correlative to DNMT family (DNMT1 r = 0.20, p < 0.01; DNMT3A r = 0.26, p < 0.001; DNMT3B r = 0.03, p = 0.57, respectively). NDRG1 expression was significantly inverse correlated with invasion depth (p = 0.023), but DNMT1 was significantly positive correlated with invasion depth (p = 0.049). DNMT3B was significantly correlated with the degree of tumor cell differentiation (p = 0.030). However, there was no association between the expression of DNMT3A and clinicopathological features. The KM plotter showed that NDRG1 (HR = 0.95, 95% CI [0.8–1.12], p = 0.53) and DNMT1 (HR = 1.04, 95% CI [0.88–1.23], p = 0.67) had no association with prognosis of GC patients, while, DNMT3A (p = 0.0064) and DNMT3B (p = 0.00025) displayed significantly association. But the overall survival of high expression of NDRG1 tended to be prolonged. Conclusion These data suggest that down-regulation of NDRG1expression in GC may be due to its promoter DNA methylation via DNMT family. The demethylating agent maybe a potential target drug for GC patients.

CDCA3 is a prognostic biomarker for cutaneous melanoma and is connected with immune infiltration

“…According to studies by Chang et al., DNMT family DNA methylation may be the cause of the downregulation of NDRG1 expression in gastric cancer. Patients with stomach cancer may benefit from using a demethylating agent as a targeted medication ( 32 ). NDRG1 has significant scientific implications in both prostate cancer and glioblastoma ( 33 , 34 ).…”

Identification of a Novel Protein-Based Prognostic Model in Gastric Cancers

“…NDRG1 is a member of the NDRG family, which was involved in a variety of physiological functions such as cell differentiation [ 13 ], stress response [ 14 ], and apoptosis [ 15 ]. The RNA-seq data of gastric cancer from the TCGA database demonstrated that the mRNA expression of NDRG1 was downregulated in STAD tumor tissues and was significantly negatively correlated with invasion depth [ 16 ]. NDRG1 overexpression could significantly suppress the proliferation and invasion and could induce a G1 cell cycle arrest in AGS cells [ 17 , 18 ].…”

Regulation of RNA methylation and immune infiltration patterns by m5C regulators in head and neck squamous cell carcinoma

“…These findings highlight the m5Cdependent mutual regulation between the nuclear reader ALYREF and the m5C writer NSUN2, leading to the progression of bladder urothelial carcinoma by activating oncogenic RNA through promoting splicing and maintaining stability. DNMT3B (DNA methyltransferase 3B) is a DNA methyltransferase, which is a key enzyme in DNA methylation that can stimulate tumor cell proliferation, migration, and invasion by regulating the promoter of the regulator gene (Caputi et al, 2021;Chang et al, 2021). Research in bladder urothelial carcinoma showed that the DNMT3B-mediated methylation of the transfer inhibitory factor 1 (MTSS1) promoter can suppress its transcription at the epigenetic level (Li et al, 2016).…”