A Novel DNA Aptamer Targeting S100P Induces Antitumor Effects in Colorectal Cancer Cells.
A Novel DNA Aptamer Targeting S100P Induces Antitumor Effects in Colorectal Cancer Cells.
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DOI：
10.1089/nat.2020.0863
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发表时间：
2020-09
影响因子：
4
通讯作者：
Wenjing Sun;Lifang Luo;Daoquan Fang;Tianbin Tang;Wuhua Ni;Bichun Dai;Hongguang Sun;Lei Jiang
中科院分区：
文献类型：
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作者：
Wenjing Sun;Lifang Luo;Daoquan Fang;Tianbin Tang;Wuhua Ni;Bichun Dai;Hongguang Sun;Lei Jiang
结直肠癌（CRC）是一种常见的恶性肿瘤，预后差，生存期差。S100P作为一种Ca2+结合蛋白，在钙依赖性信号转导通路中发挥作用，参与多种生物过程。我们前期研究表明S100P在结直肠癌组织中过表达，调控结直肠癌细胞的生长、侵袭和转移。因此，S100P有望成为CRC治疗的有效靶点。适配体是短的单链寡核苷酸，可以作为特异性和高亲和力的探针，广泛用于治疗目的的靶分子。在这项研究中，我们通过SELEX工艺和高通量测序产生了一种新的抗S100P的DNA适体（AptS100P-1）。结合实验表明，AptS100P-1对S100P蛋白具有较高的亲和力。进一步实验表明，AptS100P-1在细胞培养系统中相对稳定，可用于流式细胞术分析、点印迹法和荧光显微镜分析检测S100P。此外，AptS100P-1能够与细胞结合，并在体外和体内对CRC细胞生长有抑制作用。此外，AptS100P-1抑制表达S100P的CRC细胞的迁移和上皮间质转化。这些结果提示了一种新的靶向S100P的DNA适体，这可能是靶向S100P治疗表达S100P的CRC的潜在治疗策略。
Colorectal cancer (CRC) is a prevalent malignancy with poor prognosis and survival. As a Ca2+ binding protein, S100P plays a role in calcium-dependent signal transduction pathways that involve in diverse biological processes. Our previous studies have shown that S100P is overexpressed in CRC tissues and regulates cell growth, invasion, and metastasis in CRC. Therefore, S100P is expected to be an effective target for CRC therapy. Aptamers are short single-stranded oligonucleotides that could serve as specific and high-affinity probes to a wide range of target molecules for therapeutic purposes. In this study, we generated a novel DNA aptamer against S100P (AptS100P-1) by way of the SELEX process and high-throughput sequencing. The binding assay showed that AptS100P-1 had a high affinity for S100P protein. Further experiments indicated that AptS100P-1 is relatively stable in a cell culture system and could be used in flow cytometry analysis, dot blot assay, and fluorescence microscopy analysis to detect S100P. Moreover, AptS100P-1 was capable of binding to cells and had an inhibitory effect on CRC cell growth in vitro and in vivo. Also, AptS100P-1 inhibited the migration and epithelial-mesenchymal transition of CRC cells expressing S100P. These results indicate a novel DNA aptamer targeting S100P, which might be a potential therapeutic strategy for targeting S100P against S100P-expressing CRC.