AKT inhibits the phosphorylation level of H2A at Tyr57 via CK2α to promote the progression of gastric cancer.

BACKGROUND

Histone H2A and its variants have an important effect on DNA damage repair and cancer development. Protein kinase B (AKT) can regulate various cellular functions and play critical roles in the progression of different cancers. However, the interaction mechanism of H2A with AKT in gastric cancer (GC) has not been reported. A series of experiments were carried out in the present study to investigate this issue.

METHODS

Firstly, we used western blot and immunoprecipitation assays to determine the correlation between AKT and H2A, then detected the relationship between AKT and protein kinase CK2α that can phosphorylate H2A at Tyr57 site (H2A), and next examined the interaction among AKT, CK2α, and H2A in SNU-16 cells. Subsequently, the effect of these molecules on the cellular proliferation, migration, and invasion was measured by Cell Counting Kit-8 (CCK-8), wound healing, and transwell invasion assays.

RESULTS

Our study preliminarily found that AKT was negatively correlated with H2A phosphorylation at the Tyr 57 site (H2A). It was revealed that AKT mediated the phosphorylation of CK2α at the T13 site, which decreased the affinity of CK2α with its substrate histone H2A and inhibited the level of H2A in GC cells. Furthermore, AKT-mediated CK2α phosphorylation promoted the proliferation, migration, and invasion of SNU-16 cells possibly through downregulating H2A level.

CONCLUSIONS

These findings contribute to understanding the interactions among AKT, CK2α, and H2A in GC, and provide the potential biomarkers for the diagnosis and treatment of GC.