DNA Aptamers against Vaccinia-Related Kinase (VRK) 1 Block Proliferation in MCF7 Breast Cancer Cells.
DNA Aptamers against Vaccinia-Related Kinase (VRK) 1 Block Proliferation in MCF7 Breast Cancer Cells.
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DOI：
10.3390/ph14050473
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发表时间：
2021-05-17
期刊：
影响因子：
--
通讯作者：
González VM
中科院分区：
文献类型：
--
作者：
Carrión-Marchante R;Frezza V;Salgado-Figueroa A;Pérez-Morgado MI;Martín ME;González VM
Vaccinia-related kinase（VRK）1是一种丝氨酸/苏氨酸激酶，在DNA损伤反应（DDR）中起重要作用，磷酸化参与该过程的一些蛋白质，如53 BP 1、NBS 1或H2 AX，以及在细胞周期进程中。此外，VRK 1在许多癌症类型中过表达，其与预后不良的相关性已被确定，表明VRK 1是肿瘤学中的新治疗靶点。使用体外选择，从ssDNA文库中选择VRK 1的高亲和力DNA适体。使用酶联寡核苷酸测定法（ELISA）监测选择，并对所选适体群体进行克隆和测序。选择并表征了三种适体。这些适体识别蛋白激酶VRK 1的亲和力在纳摩尔范围内，并表现出高灵敏度。此外，用这些适体处理MCF 7乳腺细胞系导致细胞周期蛋白D1水平降低，并通过G1期阻滞抑制细胞周期进展，从而诱导细胞凋亡。这些结果表明，这些适体是VRK 1的特异性抑制剂，可能被开发为用于治疗癌症的潜在药物。
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.
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影响因子：
--
作者：
Lee N;Kwon JH;Kim YB;Kim SH;Park SJ;Xu W;Jung HY;Kim KT;Wang HJ;Choi KY
通讯作者：
Choi KY
影响因子：
3.3
作者：
Molitor TP;Traktman P
通讯作者：
Traktman P
影响因子：
3.5
作者：
Lopez-Sanchez, Inmaculada;Valbuena, Alberto;Lazo, Pedro A.
通讯作者：
Lazo, Pedro A.
DOI：
10.1007/s00018-018-2811-2
发表时间：
2018-07
期刊：
Cellular and molecular life sciences : CMLS
影响因子：
--
作者：
Campillo-Marcos I;Lazo PA
通讯作者：
Lazo PA
影响因子：
3.7
作者：
Mon AM;MacKinnon AC Jr;Traktman P
通讯作者：
Traktman P