<p>Ras-ERK1/2 Signaling Promotes The Development Of Osteosarcoma By Regulating H2BK12ac Through CBP</p>

Abstract

BackgroundH2BK12ac 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.MethodsMG-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.ResultsH2BK12ac 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.ConclusionThese findings from the study demonstrated that Ras-ERK1/2 signaling could promote the development of OS via regulating H2BK12ac through MDM2-mediated CBP degradation.

The Multifaceted Roles of RCC1 in Tumorigenesis

“…ERK1/2 can increase the expression of RCC1 through c-Jun, which affects the genome stability and promotes the development of tumors. ERK1/2 signaling could promote the development of osteosarcoma via regulating H2BK12ac ( Xu et al, 2019 ). Histone interacts with RCC1 through the H2A/H2B surface area.…”

Small Molecules Targeting HATs, HDACs, and BRDs in Cancer Therapy

“…Regarding H2A, Hat1 knockdown- or Tip60 abrogation-mediated downregulation of HeLa cell H2A lysine 5 acetylation (H2AK5ac) decreases HeLa cell colony size, suggesting that this acetylation can regulate cell proliferation ( 9 ). Furthermore, Ras-ERK1/2 pathway activation-induced osteosarcoma proliferation and migration co-occurs with downregulated H2BK12ac, a phenotype rescued by HDAC1 knockdown-mediated H2BK12ac restoration ( 10 ). Relative to other types of histone acetylation, the H2BK20ac modification preferentially accumulates at promoters of cell type-specific genes, indicating a role in regulating cell-specific functions ( 11 ).…”

Upregulation of miR-101a Suppresses Chronic Renal Fibrosis by Regulating KDM3A via Blockade of the YAP-TGF-β-Smad Signaling Pathway

“…ChIP was performed with the use of an EZ-Magna ChIP kit (EMD Millipore, Billerica, MA, USA) as previously described. 30 In brief, HK2 cells were first subjected to fixation with 4% paraformaldehyde and a 10-min period of incubation with glycine to allow the production of DNA-protein cross-linking. Then, the cells were washed twice with PBS and lysed with SDS lysis buffer (Upstate Biotechnology, Lake Placid, NY, USA).…”