K-Ras-ERK1/2 accelerates lung cancer cell development via mediating H3K18ac through the MDM2-GCN5-SIRT7 axis

Context: H3K18ac is linked to gene expression and DNA damage. Nevertheless, whether H3K18ac participates in regulating Ras-ERK1/2-affected lung cancer cell phenotypes remains unclear. Objective: We explored the effects of H3K18ac on Ras-ERK1/2-affected lung cancer cell phenotypes. Material and metho...

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Autores principales:	Ziming Cheng, Xiufeng Li, Shizhen Hou, Yubing Wu, Yi Sun, Bing Liu
Formato:	article
Lenguaje:	EN
Publicado:	Taylor & Francis Group 2019
Materias:	k-ras nci-h2126 cells cell proliferation migration erk1/2 downstream factors Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/4e8ad3df0db042418be82e2594026467
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spelling	oai:doaj.org-article:4e8ad3df0db042418be82e25940264672021-11-17T14:21:56ZK-Ras-ERK1/2 accelerates lung cancer cell development via mediating H3K18ac through the MDM2-GCN5-SIRT7 axis1388-02091744-511610.1080/13880209.2019.1672756https://doaj.org/article/4e8ad3df0db042418be82e25940264672019-01-01T00:00:00Zhttp://dx.doi.org/10.1080/13880209.2019.1672756https://doaj.org/toc/1388-0209https://doaj.org/toc/1744-5116Context: H3K18ac is linked to gene expression and DNA damage. Nevertheless, whether H3K18ac participates in regulating Ras-ERK1/2-affected lung cancer cell phenotypes remains unclear. Objective: We explored the effects of H3K18ac on Ras-ERK1/2-affected lung cancer cell phenotypes. Material and methods: NCI-H2126 cells were transfected with, pEGFP-K-RasWT and pEGFP-K-RasG12V/T35S plasmids for 48 h, and transfection with pEGFP-N1 served as a blank control. Then H3K18ac and AKT and ERK1/2 pathways-associated factors were examined. Different amounts of the H3K18Q (0.5, 1, and 2 μg) plasmids and RasG12V/T35S were co-transfected into NCI-H2126 cells, cell viability, cell colonies and migration were analyzed for exploring the biological functions of H3K18ac in NCI-H2126 cells. The ERK1/2 pathway downstream factors were detected by RT-PCR and ChIP assays. The regulatory functions of SIRT7, GCN5 and MDM2 in Ras-ERK1/2-regulated H3K18ac expression were finally uncovered. Results: RasG12V/T35S transfection decreased the expression of H3K18ac about 2.5 times compared with the pEGFP-N1 transfection group, and activated ERK1/2 and AKT pathways. Moreover, H3K18ac reduced cell viability, colonies, migration, and altered ERK1/2 downstream transcription in NCI-H2126 cells. Additionally, SIRT7 knockdown increased H3K18ac expression and repressed cell viability, migration and the percentage of cells in S phase by about 50% compared to the control group, as well as changed ERK1/2 downstream factor expression. Besides, Ras-ERK1/2 decreased H3K18ac was linked to MDM2-regulated GCN5 degradation. Conclusion: These observations disclosed that Ras-ERK1/2 promoted the development of lung cancer via decreasing H3K18ac through MDM2-mediated GCN5 degradation. These findings might provide a new therapeutic strategy for lung cancer.Ziming ChengXiufeng LiShizhen HouYubing WuYi SunBing LiuTaylor & Francis Grouparticlek-rasnci-h2126 cellscell proliferationmigrationerk1/2 downstream factorsTherapeutics. PharmacologyRM1-950ENPharmaceutical Biology, Vol 57, Iss 1, Pp 701-709 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	k-ras nci-h2126 cells cell proliferation migration erk1/2 downstream factors Therapeutics. Pharmacology RM1-950
spellingShingle	k-ras nci-h2126 cells cell proliferation migration erk1/2 downstream factors Therapeutics. Pharmacology RM1-950 Ziming Cheng Xiufeng Li Shizhen Hou Yubing Wu Yi Sun Bing Liu K-Ras-ERK1/2 accelerates lung cancer cell development via mediating H3K18ac through the MDM2-GCN5-SIRT7 axis
description	Context: H3K18ac is linked to gene expression and DNA damage. Nevertheless, whether H3K18ac participates in regulating Ras-ERK1/2-affected lung cancer cell phenotypes remains unclear. Objective: We explored the effects of H3K18ac on Ras-ERK1/2-affected lung cancer cell phenotypes. Material and methods: NCI-H2126 cells were transfected with, pEGFP-K-RasWT and pEGFP-K-RasG12V/T35S plasmids for 48 h, and transfection with pEGFP-N1 served as a blank control. Then H3K18ac and AKT and ERK1/2 pathways-associated factors were examined. Different amounts of the H3K18Q (0.5, 1, and 2 μg) plasmids and RasG12V/T35S were co-transfected into NCI-H2126 cells, cell viability, cell colonies and migration were analyzed for exploring the biological functions of H3K18ac in NCI-H2126 cells. The ERK1/2 pathway downstream factors were detected by RT-PCR and ChIP assays. The regulatory functions of SIRT7, GCN5 and MDM2 in Ras-ERK1/2-regulated H3K18ac expression were finally uncovered. Results: RasG12V/T35S transfection decreased the expression of H3K18ac about 2.5 times compared with the pEGFP-N1 transfection group, and activated ERK1/2 and AKT pathways. Moreover, H3K18ac reduced cell viability, colonies, migration, and altered ERK1/2 downstream transcription in NCI-H2126 cells. Additionally, SIRT7 knockdown increased H3K18ac expression and repressed cell viability, migration and the percentage of cells in S phase by about 50% compared to the control group, as well as changed ERK1/2 downstream factor expression. Besides, Ras-ERK1/2 decreased H3K18ac was linked to MDM2-regulated GCN5 degradation. Conclusion: These observations disclosed that Ras-ERK1/2 promoted the development of lung cancer via decreasing H3K18ac through MDM2-mediated GCN5 degradation. These findings might provide a new therapeutic strategy for lung cancer.
format	article
author	Ziming Cheng Xiufeng Li Shizhen Hou Yubing Wu Yi Sun Bing Liu
author_facet	Ziming Cheng Xiufeng Li Shizhen Hou Yubing Wu Yi Sun Bing Liu
author_sort	Ziming Cheng
title	K-Ras-ERK1/2 accelerates lung cancer cell development via mediating H3K18ac through the MDM2-GCN5-SIRT7 axis
title_short	K-Ras-ERK1/2 accelerates lung cancer cell development via mediating H3K18ac through the MDM2-GCN5-SIRT7 axis
title_full	K-Ras-ERK1/2 accelerates lung cancer cell development via mediating H3K18ac through the MDM2-GCN5-SIRT7 axis
title_fullStr	K-Ras-ERK1/2 accelerates lung cancer cell development via mediating H3K18ac through the MDM2-GCN5-SIRT7 axis
title_full_unstemmed	K-Ras-ERK1/2 accelerates lung cancer cell development via mediating H3K18ac through the MDM2-GCN5-SIRT7 axis
title_sort	k-ras-erk1/2 accelerates lung cancer cell development via mediating h3k18ac through the mdm2-gcn5-sirt7 axis
publisher	Taylor & Francis Group
publishDate	2019
url	https://doaj.org/article/4e8ad3df0db042418be82e2594026467
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K-Ras-ERK1/2 accelerates lung cancer cell development via mediating H3K18ac through the MDM2-GCN5-SIRT7 axis

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