HRas mutation rate is high in gastric cancer while the deep mechanism of HRasʼs oncogenic effects is unclear. The current work designed to link HRas signaling with H1.4S27ph in gastric cancer to decode the unclear mechanism in epigenetics standpoint. Ras Q61R/T35S expressing plasmids were transfected into SNU-16 cells.Western blot was conducted to check H1.4S27ph and extracellular-signal-regulatedtetrazolium bromide, colony formation, and transwell assays were carried out to see the effects of H1.4S27ph on SNU-16 cells phenotype. Chromatin immunoprecipitation was utilized to detect the interaction between H1.4S27ph and Ras downstream genes. Further, the enzymes responsible for H1.4S27 phosphorylation were studied by a quantitative reverse transcription-polymerase chain reaction and western blot. Ras mutation repressed H1.4 phosphorylation at Ser27 accompanied by ERK1/2 activation. H1.4S27ph reduced SNU-16 cells viability, colony formation, and migration. Meanwhile, H1.4S27ph regulated the transcription of Ras downstream genes. Ras-ERK1/2 signaling inhibited H1.4S27ph via inhibiting the activity of Aurora B. Aurora B exhibited H1.4S27ph-like effects on inhibiting SNU-16 cells viability, migration, and S-phase arrest. Further, Ras-ERK1/2 signaling degenerated Aurora B via mediating MDM2. H1.4S27ph worked as an anti-gastric cancer factor. It can be inhibited by activation of Ras-ERK1/2 signaling. Ras-ERK1/2 signaling repressed H1.4S27ph via MDM2-dependent degradation of Aurora B.
Background The relationship between phospholipase C ε‐1 (PLCE1) rs2274223 variant and digestive tract cancer remains inconclusive despite extensive investigations. Therefore, we performed this meta‐analysis to obtain a more credible conclusion. Methods PubMed, Medline, and Embase were systematic searched. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Results A total of 27 studies were finally included. Pooled analyses suggested that PLCE1 rs2274223 variant was significantly correlated with the likelihood of esophageal cancer (dominant model: p < 0.001, OR = 0.77, 95% CI 0.72–0.83; recessive model: p < 0.001, OR = 1.28, 95% CI 1.12–1.45; additive model: p < 0.001, OR = 1.20, 95% CI 1.11–1.29; allele model: p < 0.001, OR = 0.80, 95% CI 0.74–0.88) and gastric cancer (recessive model: p = 0.001, OR = 1.27, 95% CI 1.10–1.47; allele model: p = 0.03, OR = 0.88, 95% CI 0.78–0.98) in overall population. Further subgroup analyses showed that the positive results were mainly driven by the East Asians. However, no positive results were detected in Caucasians and West Asians. Conclusion Our findings indicated that the PLCE1 rs2274223 variant might serve as a promising genetic biomarker of esophageal and gastric cancer in East Asians.
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