KRas-ERK signalling promotes the onset and maintenance of uveal melanoma through regulating JMJD6-mediated H2A.X phosphorylation at tyrosine 39
Since DNA damage is a first incident occurred during a tumour attack, it is rational that histone H2A.X phosphorylation on tyrosine 39 (H2A.XY39ph) may act as a tumour-relevant factor. This study was aimed to test the authenticity of the hypothesis. Uveal melanoma MP65 cells were transfected for exp...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2019-12-01
|
| Series: | Artificial Cells, Nanomedicine, and Biotechnology |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/21691401.2019.1673764 |
| _version_ | 1818008672077348864 |
|---|---|
| author | Yaping Li Peng Yu Ying Zou Wenrui Cai Weixuan Sun Ning Han |
| author_facet | Yaping Li Peng Yu Ying Zou Wenrui Cai Weixuan Sun Ning Han |
| author_sort | Yaping Li |
| collection | DOAJ |
| description | Since DNA damage is a first incident occurred during a tumour attack, it is rational that histone H2A.X phosphorylation on tyrosine 39 (H2A.XY39ph) may act as a tumour-relevant factor. This study was aimed to test the authenticity of the hypothesis. Uveal melanoma MP65 cells were transfected for expression of KRas mutated. H2A.X phosphorylation and ERK1/2 was measured, and transwell experiment was performed to examine the consequents of H2A.XY39ph on MP65 cells developing and migration. Regulatory relationship between H2A.XY39ph and ERK1/2 downstream genes were measured. Moreover, whether JMJD6 and MDM2 are involved in H2A.X phosphorylation was studied. Mutation of Ras activated ERK1/2 signalling and inhibited H2A.X phosphorylation at Y39. Silence of H2A.XY39ph contributed to the regulation of MP65 cells growth, migration and transcription of ERK1/2 downstream genes, including CYR61, IGFBP3, WNT16B, NT5E, GDF15 and CARD16. The repressed H2A.X phosphorylation through Ras-ERK1/2 signalling might be through MDM2-mediated JMJD6 degradation. Our study suggested that Ras-ERK1/2 signalling inhibited H2A.X phosphorylation at Y39, which led to the uncontrolled developing and migration of uveal melanoma cells. In addition, H2A.X phosphorylation was mediated possibly through JMJD6 which could be degraded by MDM2. |
| first_indexed | 2024-04-14T05:32:21Z |
| format | Article |
| id | doaj.art-df5f898d3f964800aba3247f9c3d5fb1 |
| institution | Directory Open Access Journal |
| issn | 2169-1401 2169-141X |
| language | English |
| last_indexed | 2024-04-14T05:32:21Z |
| publishDate | 2019-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Artificial Cells, Nanomedicine, and Biotechnology |
| spelling | doaj.art-df5f898d3f964800aba3247f9c3d5fb12022-12-22T02:09:45ZengTaylor & Francis GroupArtificial Cells, Nanomedicine, and Biotechnology2169-14012169-141X2019-12-014714257426510.1080/21691401.2019.1673764KRas-ERK signalling promotes the onset and maintenance of uveal melanoma through regulating JMJD6-mediated H2A.X phosphorylation at tyrosine 39Yaping Li0Peng Yu1Ying Zou2Wenrui Cai3Weixuan Sun4Ning Han5Department of Ophthalmology, The Second Hospital of Jilin University, Changchun, PR ChinaDepartment of Ophthalmology, The Second Hospital of Jilin University, Changchun, PR ChinaDepartment of Ophthalmology, The Second Hospital of Jilin University, Changchun, PR ChinaDepartment of Ophthalmology, The Second Hospital of Jilin University, Changchun, PR ChinaDepartment of Gastrointestinal Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin University, Changchun, PR ChinaDepartment of Ophthalmology, The Second Hospital of Jilin University, Changchun, PR ChinaSince DNA damage is a first incident occurred during a tumour attack, it is rational that histone H2A.X phosphorylation on tyrosine 39 (H2A.XY39ph) may act as a tumour-relevant factor. This study was aimed to test the authenticity of the hypothesis. Uveal melanoma MP65 cells were transfected for expression of KRas mutated. H2A.X phosphorylation and ERK1/2 was measured, and transwell experiment was performed to examine the consequents of H2A.XY39ph on MP65 cells developing and migration. Regulatory relationship between H2A.XY39ph and ERK1/2 downstream genes were measured. Moreover, whether JMJD6 and MDM2 are involved in H2A.X phosphorylation was studied. Mutation of Ras activated ERK1/2 signalling and inhibited H2A.X phosphorylation at Y39. Silence of H2A.XY39ph contributed to the regulation of MP65 cells growth, migration and transcription of ERK1/2 downstream genes, including CYR61, IGFBP3, WNT16B, NT5E, GDF15 and CARD16. The repressed H2A.X phosphorylation through Ras-ERK1/2 signalling might be through MDM2-mediated JMJD6 degradation. Our study suggested that Ras-ERK1/2 signalling inhibited H2A.X phosphorylation at Y39, which led to the uncontrolled developing and migration of uveal melanoma cells. In addition, H2A.X phosphorylation was mediated possibly through JMJD6 which could be degraded by MDM2.https://www.tandfonline.com/doi/10.1080/21691401.2019.1673764Uveal melanomaK-Ras-ERK signallingH2A.XY39phMDM2JMJD6 |
| spellingShingle | Yaping Li Peng Yu Ying Zou Wenrui Cai Weixuan Sun Ning Han KRas-ERK signalling promotes the onset and maintenance of uveal melanoma through regulating JMJD6-mediated H2A.X phosphorylation at tyrosine 39 Artificial Cells, Nanomedicine, and Biotechnology Uveal melanoma K-Ras-ERK signalling H2A.XY39ph MDM2 JMJD6 |
| title | KRas-ERK signalling promotes the onset and maintenance of uveal melanoma through regulating JMJD6-mediated H2A.X phosphorylation at tyrosine 39 |
| title_full | KRas-ERK signalling promotes the onset and maintenance of uveal melanoma through regulating JMJD6-mediated H2A.X phosphorylation at tyrosine 39 |
| title_fullStr | KRas-ERK signalling promotes the onset and maintenance of uveal melanoma through regulating JMJD6-mediated H2A.X phosphorylation at tyrosine 39 |
| title_full_unstemmed | KRas-ERK signalling promotes the onset and maintenance of uveal melanoma through regulating JMJD6-mediated H2A.X phosphorylation at tyrosine 39 |
| title_short | KRas-ERK signalling promotes the onset and maintenance of uveal melanoma through regulating JMJD6-mediated H2A.X phosphorylation at tyrosine 39 |
| title_sort | kras erk signalling promotes the onset and maintenance of uveal melanoma through regulating jmjd6 mediated h2a x phosphorylation at tyrosine 39 |
| topic | Uveal melanoma K-Ras-ERK signalling H2A.XY39ph MDM2 JMJD6 |
| url | https://www.tandfonline.com/doi/10.1080/21691401.2019.1673764 |
| work_keys_str_mv | AT yapingli kraserksignallingpromotestheonsetandmaintenanceofuvealmelanomathroughregulatingjmjd6mediatedh2axphosphorylationattyrosine39 AT pengyu kraserksignallingpromotestheonsetandmaintenanceofuvealmelanomathroughregulatingjmjd6mediatedh2axphosphorylationattyrosine39 AT yingzou kraserksignallingpromotestheonsetandmaintenanceofuvealmelanomathroughregulatingjmjd6mediatedh2axphosphorylationattyrosine39 AT wenruicai kraserksignallingpromotestheonsetandmaintenanceofuvealmelanomathroughregulatingjmjd6mediatedh2axphosphorylationattyrosine39 AT weixuansun kraserksignallingpromotestheonsetandmaintenanceofuvealmelanomathroughregulatingjmjd6mediatedh2axphosphorylationattyrosine39 AT ninghan kraserksignallingpromotestheonsetandmaintenanceofuvealmelanomathroughregulatingjmjd6mediatedh2axphosphorylationattyrosine39 |