Neuronal pentraxin II (NPTX2) hypermethylation promotes cell proliferation but inhibits cell cycle arrest and apoptosis in gastric cancer cells by suppressing the p53 signaling pathway

Abstract

Gastric cancer is a considerable health burden worldwide. DNA methylation, a major epigenetic phenomenon, is closely related to the pathogenesis of cancer. Neuronal pentraxin II (NPTX2) has been found to be hypermethylated in several cancers such as glioblastoma and pancreatic cancer. However, the roles of NPTX2 in gastric cancer have not been reported. To explore this issue, NPTX2 expression in gastric cancer cells was assessed by western blot and quantitative real-time polymerase chain reaction (qRT-PCR). The methylation analysis of NPTX2 was performed by qRT-PCR as well as methylation-specific PCR (MS-PCR). The effects of NPTX2 on gastric cancer cell proliferation, apoptosis and cell cycle were detected by colony formation, CCK-8 and flow cytometry assays, respectively. The interaction of NPTX2 with the p53 signaling pathway was evaluated by western blot. Our study found the down-regulated expression of NPTX2 in gastric cancer cells compared with human gastric mucosal cells. In addition, the hypermethylation of NPTX2 was observed in gastric cancer cells, which was correlated with the low expression of NPTX2. Moreover, NPTX2 inhibited gastric cancer cell proliferation, inhibited apoptosis and induced cell cycle arrest. Furthermore, NPTX2 enhanced the protein expression of p53, p21 and PTEN to activate the p53 signaling pathway. Therefore, NPTX2 hypermethylation caused the downregulation of NPTX2 expression, which could promote cell proliferation, inhibit apoptosis and cause cell cycle arrest in gastric cancer cells by suppressing the p53 signaling pathway. Therefore, NPTX2 may be crucial for the progression of gastric cancer.

Promoter Hypomethylation of TGFBR3 as a Risk Factor of Alzheimer’s Disease: An Integrated Epigenomic-Transcriptomic Analysis

“…Applying CFG analysis and expression cross-validation in different brain regions, we identified six candidate risk genes for AD. NPTX2 belongs to the neuronal pentraxin family, whose promoter was frequently highly methylated in many solid tumors ( Park et al, 2007 ; Shukla et al, 2013 ; Rasmussen et al, 2017 ; Alholle et al, 2013 ; Xu et al, 2021a ). Decreased NPTX2 level has been reported to be associated with diverse neurological diseases, including Alzheimer’s disease, anxiety, vascular dementia, Parkinson’s disease and ischemia ( Moran et al, 2008 ; Chang et al, 2018 ; Cai et al, 2019 ; Shao et al, 2020 ; Libiger et al, 2021 ).…”

Dysregulation of Synaptic Signaling Genes Is Involved in Biology of Uterine Leiomyoma

“…NPTX2 (neuronal pentraxin 2) is also a member of the highly conserved pentraxin protein group and was previously associated with neurodegenerative diseases [41]. Additionally, it was also previously observed that NPTX2 hypermethylation inhibits cell cycle arrest and apoptosis in gastric cancers via p53 suppression [42], which in turn suggests a possible association of NPTX2 with epigenetic regulation. Synaptic receptors CHRM2 (cholinergic receptor muscarinic 2) and DRD2 (dopamine receptor D2) have also been listed at significantly enriched terms in GO analysis.…”

Role of sirtuin 1 in the brain development in congenital hypothyroidism rats via the regulation of p53 signaling pathway

“…Previous studies have shown that the p53 signaling pathway plays a vital role in processes such as apoptosis and cell cycle regulation [ 32 , 33 ]. Current evidence suggests that p53 encodes a sequence-specific transcription factor that controls the expression of genes whose products (such as Bax; PUMA,p53-upregulated modulator of apoptosis) mediate apoptosis [ 34 , 35 ].…”