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.
Background: Ras-PI3K pathway aberrant activation plays an important role in the occurrence and development of osteosarcoma. This study investigated the functions of Ras-PI3K pathway specific activation on histone H2A phosphorylation at threonine 120 (H2A T120ph) in osteosarcoma cells, along with the possible internal molecular mechanisms. Methods: Cell transfection was done to alter Ras G12V/Y40C , H2A T120ph and vaccinia-related kinase 1 (VRK1) expression. Then, cell viability, proliferation, migration and cell cycle distribution were assessed, respectively. qRT-PCR was utilized to measure the VRK1 and Ras-PI3K pathway downstream genes (CYR61, IGFBP3, WNT16B, NT5E, GDF15 and CARD16) expression. Chromatin immunoprecipitation (ChIP) was conducted to evaluate the input levels of H2A T120ph and VRK1 in the promoter regions of Ras-PI3K pathway downstream genes. Results: Ras-PI3K specific activation promoted histone H2A T120ph. H2A T120ph participated in the oncogenic functions of Ras-PI3K pathway on osteosarcoma by modulating the transcription of Ras-PI3K-targeted genes. Moreover, VRK1 contributed to the Ras-PI3K specific activation-induced up-regulation of H2A T120ph and osteosarcoma progression. Ras-PI3K pathway-specific activation-induced up-regulation of H2A T120ph was achieved by up-regulation of VRK1. Conclusions: Ras-PI3K pathway activation promoted osteosarcoma progression might be via up-regulating VRK1-mediated H2A T120ph. We proposed that VRK1 and H2A T120ph could be the potential targets for osteosarcoma diagnosis and treatment. HIGHLIGHTS 1. H2A T120ph is specifically promoted by Ras-PI3K pathway activation. 2. H2A T120ph joins in the oncogenic effects of Ras-PI3K pathway on osteosarcoma. 3. H2A T120ph regulates the transcription of Ras-PI3K-targeted genes. 4. VRK1 takes part in the regulatory function of Ras-PI3K pathway on H2A T120ph .
The Editor-in-Chief and Publisher of Cancer Management and Research wish to issue an Expression of Concern for the published article.After publication of article, Ras-ERK1/2 Signaling Promotes The Development Of Osteosarcoma By Regulating H2BK12ac Through CBP; Xu X, Yu H, Xu Y. Cancer Management and Research 2019;11:9153-9163, questions about the scientific integrity of the article content were brought to the Publisher and Editor's attention. We have reached out to the authors requesting that they supply information that would confirm the article's integrity, but the authors have not responded to our queries within the requested timeframe. Therefore, as we continue to work through the issues raised, we advise readers to interpret the information presented in the article with due caution.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.