Background
H2BK12ac is an important histone acetylation pattern of H2B, which has been reported in several cancers. However, whether H2BK12ac joins in Ras-ERK1/2 activation-induced osteosarcoma (OS) cell behaviors remain unclear. The study explored this peradventure and revealed the underlying mechanism.
Conclusion
These findings from the study demonstrated that Ras-ERK1/2 signaling could promote the development of OS via regulating H2BK12ac through MDM2-mediated CBP degradation.
Methods
MG-63 cells were transfected with pEGFP-N1, pEGFP-RasWT and pEGFP-K-RasG12V/T35S, H2BK12ac and ERK1/2 expression levels were analyzed by Western blot. Effects of H2BK12ac on cell viability, migration, colony formation and cell cycle were investigated by MTT, Transwell, soft-agar colony formation and flow cytometry assays. RT-qPCR and ChIP were performed to study the effect of H2BK12ac and CBP on ERK1/2-downstream gene transcriptions.
Results
H2BK12ac was specifically down-regulated by Ras-ERK1/2 activation in MG-63 cells. Down-regulated H2BK12ac participated in regulating cell proliferation and migration of MG-63 cells, meanwhile, affected the transcription of ERK1/2-downstream genes. Additionally, silence of HDAC1 up-regulated H2BK12ac expression, and inhibited the promoting effect of Ras-ERK1/2 on MG-63 cells' proliferation, migration and RNA expression levels of ERK1/2-downstream genes. Further, the degradation of CBP mediated by MDM2 was discovered to be linked to Ras-ERK1/2 activation-induced H2BK12ac down-regulation.