Back to Journals » Cancer Management and Research » Volume 11

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

Authors Xu X, Yu H, Xu Y

Received 14 June 2019

Accepted for publication 27 August 2019

Published 24 October 2019 Volume 2019:11 Pages 9153—9163

DOI https://doi.org/10.2147/CMAR.S219535

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Cristina Weinberg

Peer reviewer comments 2

Editor who approved publication: Dr Chien-Feng Li


Xianlun Xu,1,2 Hao Yu,1,2 Yupeng Xu3

1Department of Traumatology, Jining No.1 People’s Hospital, Jining 272011, Shandong, People’s Republic of China; 2Affiliated Jining No.1 People’s Hospital of Jining Medical University, Jining Medical University, Jining 272067, Shandong, People’s Republic of China; 3Department of Orthopedics, Jining Bone Fracture Hospital, Jining 272000, Shandong, People’s Republic of China

Correspondence: Xianlun Xu
Department of Traumatology, Jining No.1 People’s Hospital, No. 6 Jiankang Road, Jining 272011, Shandong, People’s Republic of China
Email cuanzhidao0058rku@163.com
Yupeng Xu
Department of Orthopedics, Jining Bone Fracture Hospital, No. 28 Rencheng Road, Jining 272000, Shandong, People’s Republic of China
Tel +86-0537-221272
Email xuyupeng213@sina.com

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.
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.
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.

Keywords: osteosarcoma, Ras-ERK1/2 signaling, H2BK12ac, HDAC1, CBP, MDM2

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]