Selection and characterization of novel DNA aptamers targeting colorectal cancer cells with malignant potential

IF 3.8 2区化学 Q1 BIOCHEMICAL RESEARCH METHODS

Analytical and Bioanalytical Chemistry Pub Date : 2025-09-02 DOI:10.1007/s00216-025-06091-9

Yinuo Ma, Qun Wang, Shihan Sun, Yanxi Li, Rui Wang, Haihui Yang, Dian Wang, Yangyang Hao, Yujing Tong, Wanming Li

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引用次数: 0

Abstract

Colorectal cancer (CRC) is associated with high morbidity and mortality rates worldwide. Therefore, early diagnosis and treatment are of great significance for improving the survival rate of CRC patients. Herein, we performed subtractive cell-SELEX using two cell lines (LS174T and CL187) with the same genetic background but different malignant potentials for the target and negative cells. Two aptamers LS1 and LS52 showed high affinity with target LS174T cells and high specificity for CRC cells with malignant potential, and exhibited good biological stability. In addition, we found that aptamer LS1 had the effect of promoting in vitro proliferation and monoclonal formation of CRC cells, and upregulated the expression of proliferation related proteins. Based on the high affinity of aptamer LS52, using LS52 as a molecular probe could effectively distinguish clinical CRC tissues and adjacent normal tissues, CRC metastatic tissues and non-metastatic tissues. Analysis of protein expression in magnetic bead sorted cells showed that the expression of malignant potential related proteins in LS52^high cells was higher than that in LS52^low cells. Finally, a cell membrane protein SRSF6 was identified as the target of aptamer LS52, which may serve as a new molecular target for CRC. Therefore, our work provides a systematic novel approach of studying potential biomarkers and a promising tool for cancer diagnosis and therapy.

Graphical Abstract

查看原文本刊更多论文

靶向结直肠癌恶性肿瘤细胞的新型DNA适体的选择和鉴定。

结直肠癌（CRC）在世界范围内具有很高的发病率和死亡率。因此，早期诊断和治疗对于提高结直肠癌患者的生存率具有重要意义。在此，我们使用两种具有相同遗传背景但靶细胞和阴性细胞恶性潜能不同的细胞系（LS174T和CL187）进行减法细胞selex。两个适配体LS1和LS52对靶细胞LS174T具有高亲和力，对有恶性潜能的CRC细胞具有高特异性，具有良好的生物学稳定性。此外，我们发现适体LS1具有促进CRC细胞体外增殖和单克隆形成的作用，并上调增殖相关蛋白的表达。基于适配体LS52的高亲和力，使用LS52作为分子探针可以有效区分临床CRC组织与邻近正常组织、CRC转移组织与非转移组织。磁珠分选细胞中蛋白表达分析显示，恶性潜能相关蛋白在LS52high细胞中的表达高于LS52low细胞。最后，我们确定了一个细胞膜蛋白SRSF6作为适体LS52的靶点，这可能是CRC的一个新的分子靶点。因此，我们的工作提供了一种系统的新方法来研究潜在的生物标志物，并为癌症诊断和治疗提供了一个有前途的工具。

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来源期刊

Analytical and Bioanalytical Chemistry 化学-分析化学

CiteScore

8.00

自引率

4.70%

发文量

638

审稿时长

2.1 months

期刊介绍： Analytical and Bioanalytical Chemistry’s mission is the rapid publication of excellent and high-impact research articles on fundamental and applied topics of analytical and bioanalytical measurement science. Its scope is broad, and ranges from novel measurement platforms and their characterization to multidisciplinary approaches that effectively address important scientific problems. The Editors encourage submissions presenting innovative analytical research in concept, instrumentation, methods, and/or applications, including: mass spectrometry, spectroscopy, and electroanalysis; advanced separations; analytical strategies in “-omics” and imaging, bioanalysis, and sampling; miniaturized devices, medical diagnostics, sensors; analytical characterization of nano- and biomaterials; chemometrics and advanced data analysis.