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抗痘苗相关激酶（VRK）1的DNA适配体可阻断MCF7乳腺癌细胞的增殖。

DNA Aptamers against Vaccinia-Related Kinase (VRK) 1 Block Proliferation in MCF7 Breast Cancer Cells.

作者信息

Carrión-Marchante Rebeca, Frezza Valerio, Salgado-Figueroa Ana, Pérez-Morgado M Isabel, Martín M Elena, González Víctor M

机构信息

Grupo de Aptámeros, Departamento de Bioquímica-Investigación, IRYCIS-Hospital Universitario Ramón y Cajal, Carretera de Colmenar Viejo Km. 9.100, 28034 Madrid, Spain.

出版信息

Pharmaceuticals (Basel). 2021 May 17;14(5):473. doi: 10.3390/ph14050473.

DOI:10.3390/ph14050473
PMID:34067799
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8156982/
Abstract

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.

摘要

痘苗相关激酶（VRK）1是一种丝氨酸/苏氨酸激酶，在DNA损伤反应（DDR）中发挥重要作用，可磷酸化参与该过程的一些蛋白质，如53BP1、NBS1或H2AX，并且在细胞周期进程中也发挥作用。此外，VRK1在多种癌症类型中过表达，并且已确定其与不良预后相关，这表明VRK1是肿瘤学中的一个新治疗靶点。通过体外筛选，从单链DNA文库中筛选出了与VRK1具有高亲和力的DNA适配体。使用酶联寡核苷酸分析（ELONA）监测筛选过程，并对所选的适配体群体进行克隆和测序。筛选出并鉴定了三种适配体。这些适配体以纳摩尔范围内的亲和力识别蛋白激酶VRK1，并表现出高灵敏度。此外，用这些适配体处理MCF7乳腺癌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程，从而诱导细胞凋亡。这些结果表明，这些适配体是VRK1的特异性抑制剂，可能被开发为治疗癌症的潜在药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2722/8156982/fa2d21ca6de5/pharmaceuticals-14-00473-g007.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2722/8156982/7ff2c15a3d84/pharmaceuticals-14-00473-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2722/8156982/c0a8002f23ff/pharmaceuticals-14-00473-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2722/8156982/caaf70887e56/pharmaceuticals-14-00473-g004.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2722/8156982/fa2d21ca6de5/pharmaceuticals-14-00473-g007.jpg

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Clarithromycin effectively enhances doxorubicin-induced cytotoxicity and apoptosis in MCF7 cells through dysregulation of autophagy.克拉霉素通过调控自噬有效地增强了多柔比星诱导的 MCF7 细胞的细胞毒性和细胞凋亡。
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