Ras-ERK1/2 signaling participates in the progression of gastric cancer through repressing Aurora B-mediated H1.4 phosphorylation at Ser27

HRas mutation rate is high in gastric cancer while the deep mechanism of HRas's 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-regulated kinase 1/2 (ERK1/2) expression. 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium 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.