Ras-ERK1/2 Signaling Promotes The Development Of Osteosarcoma By Regulating H2BK12ac Through CBP
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, Shando...
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2019-10-01
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| Series: | Cancer Management and Research |
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| Online Access: | https://www.dovepress.com/ras-erk12-signaling-promotes-the-development-of-osteosarcoma-by-regula-peer-reviewed-article-CMAR |
| _version_ | 1819076215505420288 |
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| author | Xu X Yu H Xu Y |
| author_facet | Xu X Yu H Xu Y |
| author_sort | Xu X |
| collection | DOAJ |
| description | 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 ChinaCorrespondence: Xianlun XuDepartment of Traumatology, Jining No.1 People’s Hospital, No. 6 Jiankang Road, Jining 272011, Shandong, People’s Republic of ChinaEmail cuanzhidao0058rku@163.comYupeng XuDepartment of Orthopedics, Jining Bone Fracture Hospital, No. 28 Rencheng Road, Jining 272000, Shandong, People’s Republic of ChinaTel +86-0537-221272Email xuyupeng213@sina.comBackground: 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 |
| first_indexed | 2024-12-21T18:37:46Z |
| format | Article |
| id | doaj.art-4d9552f0ce234bbcaa847dc185879f79 |
| institution | Directory Open Access Journal |
| issn | 1179-1322 |
| language | English |
| last_indexed | 2024-12-21T18:37:46Z |
| publishDate | 2019-10-01 |
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| series | Cancer Management and Research |
| spelling | doaj.art-4d9552f0ce234bbcaa847dc185879f792022-12-21T18:54:06ZengDove Medical PressCancer Management and Research1179-13222019-10-01Volume 119153916349296Ras-ERK1/2 Signaling Promotes The Development Of Osteosarcoma By Regulating H2BK12ac Through CBPXu XYu HXu YXianlun 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 ChinaCorrespondence: Xianlun XuDepartment of Traumatology, Jining No.1 People’s Hospital, No. 6 Jiankang Road, Jining 272011, Shandong, People’s Republic of ChinaEmail cuanzhidao0058rku@163.comYupeng XuDepartment of Orthopedics, Jining Bone Fracture Hospital, No. 28 Rencheng Road, Jining 272000, Shandong, People’s Republic of ChinaTel +86-0537-221272Email xuyupeng213@sina.comBackground: 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, MDM2https://www.dovepress.com/ras-erk12-signaling-promotes-the-development-of-osteosarcoma-by-regula-peer-reviewed-article-CMAROsteosarcomaRas-ERK1/2 signalingH2BK12acHDAC1CBPMDM2 |
| spellingShingle | Xu X Yu H Xu Y Ras-ERK1/2 Signaling Promotes The Development Of Osteosarcoma By Regulating H2BK12ac Through CBP Cancer Management and Research Osteosarcoma Ras-ERK1/2 signaling H2BK12ac HDAC1 CBP MDM2 |
| title | Ras-ERK1/2 Signaling Promotes The Development Of Osteosarcoma By Regulating H2BK12ac Through CBP |
| title_full | Ras-ERK1/2 Signaling Promotes The Development Of Osteosarcoma By Regulating H2BK12ac Through CBP |
| title_fullStr | Ras-ERK1/2 Signaling Promotes The Development Of Osteosarcoma By Regulating H2BK12ac Through CBP |
| title_full_unstemmed | Ras-ERK1/2 Signaling Promotes The Development Of Osteosarcoma By Regulating H2BK12ac Through CBP |
| title_short | Ras-ERK1/2 Signaling Promotes The Development Of Osteosarcoma By Regulating H2BK12ac Through CBP |
| title_sort | ras erk1 2 signaling promotes the development of osteosarcoma by regulating h2bk12ac through cbp |
| topic | Osteosarcoma Ras-ERK1/2 signaling H2BK12ac HDAC1 CBP MDM2 |
| url | https://www.dovepress.com/ras-erk12-signaling-promotes-the-development-of-osteosarcoma-by-regula-peer-reviewed-article-CMAR |
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