Increased mutational burden and EBV load have been revealed from normal tissues to Epstein-Barr virus (EBV)-associated gastric carcinomas (EBVaGCs). BPLF1, encoded by EBV, is a lytic cycle protein ...with deubiquitinating activity has been found to participate in disrupting repair of DNA damage. We first confirmed that BPLF1 gene in gastric cancer (GC) significantly increased the DNA double strand breaks (DSBs). Ubiquitination mass spectrometry identified histones as BPLF1 interactors and potential substrates, and co-immunoprecipitation and in vitro experiments verified that BPLF1 regulates H2Bub by targeting Rad6. Over-expressing Rad6 restored H2Bub but partially reduced γ-H2AX, suggesting that other downstream DNA repair processes were affected. mRNA expression of BRCA2 were significantly down-regulated by next-generation sequencing after over-expression of BPLF1, and over-expression of p65 facilitated the repair of DSBs. We demonstrated BPLF1 may lead to the accumulation of DSBs by two pathways, reducing H2B ubiquitination (H2Bub) and blocking homologous recombination which may provide new ideas for the treatment of gastric cancer.
Objectives
To assess the region‐specific relative risk of cardia/non‐cardia gastric cancer (CGC/NCGC) associated with Helicobacter pylori (H. pylori) and quantify its contribution to gastric cancer ...burden using population attributable fraction (PAF).
Methods
PubMed, EMBASE, Web of Science, and Cochrane Central databases were searched by two reviewers until April 20, 2022. The association between H. pylori infection and NCGC/CGC was assessed using pooled odds ratios (ORs) with 95% confidence intervals (CIs). PAF was calculated using the formula of H. pylori prevalence and the pooled OR.
Results
One hundred and eight studies were included. A significant association was observed between H. pylori infection and NCGC in East Asia (OR, 4.36; 95% CI: 3.54–5.37) and the West (OR, 4.03; 95% CI: 2.59–6.27). Regarding CGC, a significant association was found only in East Asia (OR, 2.86; 95% CI: 2.26–3.63), not in the West (OR, 0.80; 95% CI: 0.61–1.05). For studies with a follow‐up time of ≥10 years, pooled ORs for NCGC and CGC in East Asia were 5.58 (95% CI: 4.08–7.64) and 3.86 (95% CI: 2.69–5.55), respectively. Pooled OR for NCGC was 6.80 (95% CI: 3.78–12.25) in the West. PAFs showed that H. pylori infection accounted for 71.2% of NCGC, 60.7% of CGC in East Asia, and 73.2% of NCGC in the West.
Conclusions
Gastric cancer burden associated with H. pylori infection exhibits important geographical differences. Prolonged follow‐up period could overcome the underestimation of the magnitude of the association between H. pylori infection and CGC/NCGC. Customized strategies for H. pylori screening and eradication should be implemented to prevent gastric cancer.
While the incidence of gastric cancer has decreased worldwide in recent decades,the incidence of signetring cell carcinoma(SRCC) is rising. SRCC has a specific epidemiology and oncogenesis and has ...two forms: early gastric cancer,which can be resected endoscopically in some cases and which has a better outcome than non-SRCC,and advanced gastric cancer,which is generally thought to have a worse prognosis and lower chemosensitivity than non-SRCC. However,the prognosis of SRCC and its chemosensitivity with specific regimens are still controversial as SRCC is not specifically identified in most studies and its poor prognosis may be due to its more advanced stage. It therefore remains unclear if a specific therapeutic strategy is justified,as the benefit of perioperative chemotherapy and the value of taxanebased chemotherapy are unclear. In this review we analyze recent data on the epidemiology,oncogenesis,prognosis and specific therapeutic strategies in both early and advanced SRCC of the stomach and in hereditary diffuse gastric cancer.
Gastric cancer (GC) is the 5th most common cancer over the world. Ubiquitin protease 43 (UBP43) is a multifunctional protein with deubiquitinase activities. Abnormal expression of UBP43 has been ...reported in numerous types of malignancies. Bioinformatic analysis was performed to identify the differentially expressed genes (Fold change ≥2 or ≤ −2 and p < 0.01) in GC from the datasets downloaded from Gene Expression Omnibus and Gene Expression Profiling Interactive Analysis databases, which showed that UBP43 and stress-inducible phosphoprotein 1 (STIP1) were up-regulated in both datasets. Online databases displayed the binding of UBP43 to STIP1 and the positive correlation between the two proteins. This study aims to explore: the role of UBP43 in cell proliferation and apoptosis in GC; the relationship between UBP43 and STIP1; and whether UBP43 exerts its function via STIP1 in GC. Knockdown/overexpression stable GC cell lines were generated by transducing lentivirus carrying coding sequence/short hairpin RNA of UBP43 and puromycin selection. GC patients with higher expressions of UBP43 had poor prognosis. Loss-/gain-of-function experiments revealed that pro-proliferative and anti-apoptotic abilities of UBP43 in GC cells and xenografts. UBP43 could interact with STIP1, inhibit its ubiquitination, and promote its protein stability, thereby enhancing STIP1 expression. Moreover, STIP1 knockdown reversed the pro-proliferative ability of UBP43 in GC cells. Our study uncovers that the pro-proliferative role of UBP43 in GC development is STIP1-dependent and indicates that UBP43 may act as a potent therapeutic target in GC treatment.
•UBP43 promotes gastric cell proliferation in vitro and tumor growth in vivo.•UBP43 promotes gastric cell cycle progression but inhibits cell apoptosis in vitro.•UBP43 serves as a deubiquitinase to regulate STIP1 stability in gastric cancer.•UBP43 exerts its oncogenic role in gastric cancer through regulation of STIP1.
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