CDK11 Loss Induces Cell Cycle Dysfunction and Death of BRAF and NRAS Melanoma Cells
Cyclin dependent kinase 11 (CDK11) is a protein kinase that regulates RNA transcription, pre-mRNA splicing, mitosis, and cell death. Targeting of CDK11 expression levels is effective in the experimental treatment of breast and other cancers, but these data are lacking in melanoma. To understand CDK1...
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| Format: | Article |
| Language: | English |
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MDPI AG
2019-04-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/12/2/50 |
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| author | Rehana L. Ahmed Daniel P. Shaughnessy Todd P. Knutson Rachel I. Vogel Khalil Ahmed Betsy T. Kren Janeen H. Trembley |
| author_facet | Rehana L. Ahmed Daniel P. Shaughnessy Todd P. Knutson Rachel I. Vogel Khalil Ahmed Betsy T. Kren Janeen H. Trembley |
| author_sort | Rehana L. Ahmed |
| collection | DOAJ |
| description | Cyclin dependent kinase 11 (CDK11) is a protein kinase that regulates RNA transcription, pre-mRNA splicing, mitosis, and cell death. Targeting of CDK11 expression levels is effective in the experimental treatment of breast and other cancers, but these data are lacking in melanoma. To understand CDK11 function in melanoma, we evaluated protein and RNA levels of CDK11, Cyclin L1 and Cyclin L2 in benign melanocytes and BRAF- as well as NRAS-mutant melanoma cell lines. We investigated the effectiveness of reducing expression of this survival kinase using RNA interference on viability, clonal survival, and tumorsphere formation in melanoma cell lines. We examined the impact of CDK11 loss in BRAF-mutant melanoma on more than 700 genes important in cancer signaling pathways. Follow-up analysis evaluated how CDK11 loss alters cell cycle function in BRAF- and NRAS-mutant melanoma cells. We present data on CDK11, CCNL1 and CCNL2 mRNA expression in melanoma patients, including prognosis for survival. In sum, we found that CDK11 is necessary for melanoma cell survival, and a major impact of CDK11 loss in melanoma is to cause disruption of the cell cycle distribution with accumulation of G1- and loss of G2/M-phase cancer cells. |
| first_indexed | 2024-12-19T17:34:47Z |
| format | Article |
| id | doaj.art-c36cf854d71c4daca8db8a3ed125a87d |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-12-19T17:34:47Z |
| publishDate | 2019-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-c36cf854d71c4daca8db8a3ed125a87d2022-12-21T20:12:21ZengMDPI AGPharmaceuticals1424-82472019-04-011225010.3390/ph12020050ph12020050CDK11 Loss Induces Cell Cycle Dysfunction and Death of BRAF and NRAS Melanoma CellsRehana L. Ahmed0Daniel P. Shaughnessy1Todd P. Knutson2Rachel I. Vogel3Khalil Ahmed4Betsy T. Kren5Janeen H. Trembley6Department of Dermatology, University of Minnesota, Minneapolis, MN 55455, USAResearch Service, Minneapolis VA Health Care System, Minneapolis, MN 55417, USADepartment of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, USAMasonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USAMasonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USAMasonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USAMasonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USACyclin dependent kinase 11 (CDK11) is a protein kinase that regulates RNA transcription, pre-mRNA splicing, mitosis, and cell death. Targeting of CDK11 expression levels is effective in the experimental treatment of breast and other cancers, but these data are lacking in melanoma. To understand CDK11 function in melanoma, we evaluated protein and RNA levels of CDK11, Cyclin L1 and Cyclin L2 in benign melanocytes and BRAF- as well as NRAS-mutant melanoma cell lines. We investigated the effectiveness of reducing expression of this survival kinase using RNA interference on viability, clonal survival, and tumorsphere formation in melanoma cell lines. We examined the impact of CDK11 loss in BRAF-mutant melanoma on more than 700 genes important in cancer signaling pathways. Follow-up analysis evaluated how CDK11 loss alters cell cycle function in BRAF- and NRAS-mutant melanoma cells. We present data on CDK11, CCNL1 and CCNL2 mRNA expression in melanoma patients, including prognosis for survival. In sum, we found that CDK11 is necessary for melanoma cell survival, and a major impact of CDK11 loss in melanoma is to cause disruption of the cell cycle distribution with accumulation of G1- and loss of G2/M-phase cancer cells.https://www.mdpi.com/1424-8247/12/2/50CDK11Cyclin L1Cyclin L2cell cyclecancermelanoma |
| spellingShingle | Rehana L. Ahmed Daniel P. Shaughnessy Todd P. Knutson Rachel I. Vogel Khalil Ahmed Betsy T. Kren Janeen H. Trembley CDK11 Loss Induces Cell Cycle Dysfunction and Death of BRAF and NRAS Melanoma Cells Pharmaceuticals CDK11 Cyclin L1 Cyclin L2 cell cycle cancer melanoma |
| title | CDK11 Loss Induces Cell Cycle Dysfunction and Death of BRAF and NRAS Melanoma Cells |
| title_full | CDK11 Loss Induces Cell Cycle Dysfunction and Death of BRAF and NRAS Melanoma Cells |
| title_fullStr | CDK11 Loss Induces Cell Cycle Dysfunction and Death of BRAF and NRAS Melanoma Cells |
| title_full_unstemmed | CDK11 Loss Induces Cell Cycle Dysfunction and Death of BRAF and NRAS Melanoma Cells |
| title_short | CDK11 Loss Induces Cell Cycle Dysfunction and Death of BRAF and NRAS Melanoma Cells |
| title_sort | cdk11 loss induces cell cycle dysfunction and death of braf and nras melanoma cells |
| topic | CDK11 Cyclin L1 Cyclin L2 cell cycle cancer melanoma |
| url | https://www.mdpi.com/1424-8247/12/2/50 |
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