DNA Aptamers against Vaccinia-Related Kinase (VRK) 1 Block Proliferation in MCF7 Breast Cancer Cells
Vaccinia-related kinase (VRK) 1 is a serin/threonine kinase that plays an important role in DNA damage response (DDR), phosphorylating some proteins involved in this process such as 53BP1, NBS1 or H2AX, and in the cell cycle progression. In addition, VRK1 is overexpressed in many cancer types and it...
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| Format: | Article |
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MDPI AG
2021-05-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/14/5/473 |
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| author | Rebeca Carrión-Marchante Valerio Frezza Ana Salgado-Figueroa M. Isabel Pérez-Morgado M. Elena Martín Víctor M. González |
| author_facet | Rebeca Carrión-Marchante Valerio Frezza Ana Salgado-Figueroa M. Isabel Pérez-Morgado M. Elena Martín Víctor M. González |
| author_sort | Rebeca Carrión-Marchante |
| collection | DOAJ |
| description | Vaccinia-related kinase (VRK) 1 is a serin/threonine kinase that plays an important role in DNA damage response (DDR), phosphorylating some proteins involved in this process such as 53BP1, NBS1 or H2AX, and in the cell cycle progression. In addition, VRK1 is overexpressed in many cancer types and its correlation with poor prognosis has been determined, showing VRK1 as a new therapeutic target in oncology. Using in vitro selection, high-affinity DNA aptamers to VRK1 were selected from a library of ssDNA. Selection was monitored using the enzyme-linked oligonucleotide assay (ELONA), and the selected aptamer population was cloned and sequenced. Three aptamers were selected and characterized. These aptamers recognized the protein kinase VRK1 with an affinity in the nanomolar range and showed a high sensibility. Moreover, the treatment of the MCF7 breast cell line with these aptamers resulted in a decrease in cyclin D1 levels, and an inhibition of cell cycle progression by G1 phase arrest, which induced apoptosis in cells. These results suggest that these aptamers are specific inhibitors of VRK1 that might be developed as potential drugs for the treatment of cancer. |
| first_indexed | 2024-03-10T11:20:14Z |
| format | Article |
| id | doaj.art-a6f745f081dc4c77930a024d7218e4bf |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-10T11:20:14Z |
| publishDate | 2021-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-a6f745f081dc4c77930a024d7218e4bf2023-11-21T20:06:16ZengMDPI AGPharmaceuticals1424-82472021-05-0114547310.3390/ph14050473DNA Aptamers against Vaccinia-Related Kinase (VRK) 1 Block Proliferation in MCF7 Breast Cancer CellsRebeca Carrión-Marchante0Valerio Frezza1Ana Salgado-Figueroa2M. Isabel Pérez-Morgado3M. Elena Martín4Víctor M. González5Grupo de Aptámeros, Departamento de Bioquímica-Investigación, IRYCIS-Hospital Universitario Ramón y Cajal, Carretera de Colmenar Viejo Km. 9.100, 28034 Madrid, SpainGrupo de Aptámeros, Departamento de Bioquímica-Investigación, IRYCIS-Hospital Universitario Ramón y Cajal, Carretera de Colmenar Viejo Km. 9.100, 28034 Madrid, SpainGrupo de Aptámeros, Departamento de Bioquímica-Investigación, IRYCIS-Hospital Universitario Ramón y Cajal, Carretera de Colmenar Viejo Km. 9.100, 28034 Madrid, SpainGrupo de Aptámeros, Departamento de Bioquímica-Investigación, IRYCIS-Hospital Universitario Ramón y Cajal, Carretera de Colmenar Viejo Km. 9.100, 28034 Madrid, SpainGrupo de Aptámeros, Departamento de Bioquímica-Investigación, IRYCIS-Hospital Universitario Ramón y Cajal, Carretera de Colmenar Viejo Km. 9.100, 28034 Madrid, SpainGrupo de Aptámeros, Departamento de Bioquímica-Investigación, IRYCIS-Hospital Universitario Ramón y Cajal, Carretera de Colmenar Viejo Km. 9.100, 28034 Madrid, SpainVaccinia-related kinase (VRK) 1 is a serin/threonine kinase that plays an important role in DNA damage response (DDR), phosphorylating some proteins involved in this process such as 53BP1, NBS1 or H2AX, and in the cell cycle progression. In addition, VRK1 is overexpressed in many cancer types and its correlation with poor prognosis has been determined, showing VRK1 as a new therapeutic target in oncology. Using in vitro selection, high-affinity DNA aptamers to VRK1 were selected from a library of ssDNA. Selection was monitored using the enzyme-linked oligonucleotide assay (ELONA), and the selected aptamer population was cloned and sequenced. Three aptamers were selected and characterized. These aptamers recognized the protein kinase VRK1 with an affinity in the nanomolar range and showed a high sensibility. Moreover, the treatment of the MCF7 breast cell line with these aptamers resulted in a decrease in cyclin D1 levels, and an inhibition of cell cycle progression by G1 phase arrest, which induced apoptosis in cells. These results suggest that these aptamers are specific inhibitors of VRK1 that might be developed as potential drugs for the treatment of cancer.https://www.mdpi.com/1424-8247/14/5/473DNA aptamersanticancer aptamersVRK1breast cancercell cycle |
| spellingShingle | Rebeca Carrión-Marchante Valerio Frezza Ana Salgado-Figueroa M. Isabel Pérez-Morgado M. Elena Martín Víctor M. González DNA Aptamers against Vaccinia-Related Kinase (VRK) 1 Block Proliferation in MCF7 Breast Cancer Cells Pharmaceuticals DNA aptamers anticancer aptamers VRK1 breast cancer cell cycle |
| title | DNA Aptamers against Vaccinia-Related Kinase (VRK) 1 Block Proliferation in MCF7 Breast Cancer Cells |
| title_full | DNA Aptamers against Vaccinia-Related Kinase (VRK) 1 Block Proliferation in MCF7 Breast Cancer Cells |
| title_fullStr | DNA Aptamers against Vaccinia-Related Kinase (VRK) 1 Block Proliferation in MCF7 Breast Cancer Cells |
| title_full_unstemmed | DNA Aptamers against Vaccinia-Related Kinase (VRK) 1 Block Proliferation in MCF7 Breast Cancer Cells |
| title_short | DNA Aptamers against Vaccinia-Related Kinase (VRK) 1 Block Proliferation in MCF7 Breast Cancer Cells |
| title_sort | dna aptamers against vaccinia related kinase vrk 1 block proliferation in mcf7 breast cancer cells |
| topic | DNA aptamers anticancer aptamers VRK1 breast cancer cell cycle |
| url | https://www.mdpi.com/1424-8247/14/5/473 |
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