Retraction

Abstract

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.

Histone H1 Post-Translational Modifications: Update and Future Perspectives

“…H1.4S35p showed a tumor suppressor role as the overexpression of a mutant mimicking phosphorylation attenuated cell viability, colony formation, S-phase arrest, migration, and invasion upon mutant Ras transfection in NSCLC cell lines. A similar effect was found for the phosphorylation of H1.4 in S26 in gastric cancer cells (SNU-16), where H1.4S26p reduced cell viability, colony formation, and migration [ 103 ]. Ras mutation, accompanied by ERK1/2 activation, repressed H1.4 phosphorylation at S26 by the induction of MDM2-dependent proteasomal degradation of Aurora B.…”

“…Post-translational modifications in histone H1 have been associated with cancer, autoimmune diseases, and viral infection [ 37 , 95 , 96 , 97 , 98 , 99 , 100 , 101 , 102 , 103 ]. Different modification types in H1 have been described in disease including, phosphorylation, methylation, ubiquitylation, and citrullination.…”

“…PTMs associated with cancer have been extensively studied to find new biomarkers of cancer progression and prognosis to personalize therapeutic strategies as well as to understand the underlying mechanisms of the disease. Several phosphorylations in subtypes H1.2–H1.5 have been associated with cancer progression and prognosis [ 37 , 95 , 96 , 97 , 98 , 101 , 103 ]. Phosphorylation of H1.2 and H1.4 at T145 has been proposed as a biomarker for bladder cancer [ 95 ].…”

Study of the active ingredients and mechanism of Sparganii rhizoma in gastric cancer based on HPLC-Q-TOF–MS/MS and network pharmacology

“…Its positive expression rate in GC tissues is significantly higher than that in adjacent tissues, and it participates in the occurrence and development of GC [52][53][54] . HRAS belongs to the RAS gene family, which regulates RAF-MEK-ERK, PI3K/AKT, and other signalling pathways related to cell survival and proliferation by binding to GTP/GDP and the RAS protein to act as a molecular switch 55,56 . HRAS mutations are closely associated with the occurrence of various tumours.…”

Purinergic P2Y2 and P2X4 Receptors Are Involved in the Epithelial-Mesenchymal Transition and Metastatic Potential of Gastric Cancer Derived Cell Lines

“…This protein is involved in the regulation of G1/S transition and its overexpression has been documented in the proliferation of gastric cancer cells [61]. IGF2 has also been associated with cell proliferation and differentiation in gastric cancer [62,63]. These changes are concomitant with the downregulation of apoptotic elements such as CASP8 and CASP10.…”