Selection and identification of a novel DNA aptamer for recognizing colorectal cancer stem cells

IF 4.7 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Bioorganic Chemistry Pub Date : 2025-09-16 DOI:10.1016/j.bioorg.2025.108989

Wanming Li , Tao Bing , Qun Wang , Yanxi Li , Shihan Sun , Xin Li , Yinuo Ma , Rui Wang , Wei Ba , Xinyan Li , Dihua Shangguan , Jin Fang

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Abstract

Metastasis is one of the main causes of cancer-related deaths. Cancer stem cells (CSCs) have the ability to initiate metastasis; however, there is a lack of effective biomarkers to characterize CSC. In this study, subtractive cell-SELEX was performed using colorectal cancer (CRC) HCT116 cells with high stemness characteristics and CL187 cells with low stemness characteristics as the target and negative cells, respectively, for stemness-specific aptamers selection. Two aptamers were obtained, among which aptamer L33 had good specificity for CRC cells with stemness characteristics. Besides, aptamer L33 had excellent affinity with a Kd of 16.6 ± 2.1 nM and good temperature stability. Subsequently, we obtained two cell subpopulations by L33-based cell sorting and confirmed that the L33-positive cell subpopulation had higher expression of stemness-associated markers, stronger tumor sphere-forming capacity, chemotherapy drug tolerance, migration and invasion ability, and in vivo tumorigenicity. After confirming that aptamer L33 is closely associated with tumor stemness, we used L33 as a stem circulating tumor cell (CTC) capture probe and found a higher detection rate of L33-positive CTCs in the peripheral blood of patients with metastatic CRC, suggesting that CTC capture analysis based on L33 has a stronger ability to predict metastasis. Therefore, aptamer L33 developed in this study may provide a potential target for the diagnosis of metastatic CRC and CSC based therapy.

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一种识别结直肠癌干细胞的新型DNA适体的选择和鉴定

转移是癌症相关死亡的主要原因之一。肿瘤干细胞（CSCs）具有启动转移的能力；然而，缺乏有效的生物标志物来表征CSC。本研究分别以具有高干性特征的结直肠癌（CRC） HCT116细胞和具有低干性特征的CL187细胞为靶细胞和阴性细胞，进行了干细胞特异性适配体选择的减法细胞selex。获得两个适配体，其中适配体L33对具有干性特征的结直肠癌细胞具有良好的特异性。适体L33具有良好的亲和力，Kd值为16.6±2.1 nM，温度稳定性好。随后，我们通过基于l33的细胞分选获得了两个细胞亚群，并证实l33阳性细胞亚群具有更高的干细胞相关标志物表达、更强的肿瘤成球能力、化疗药物耐受性、迁移和侵袭能力以及体内致瘤性。在确认适体L33与肿瘤干性密切相关后，我们将L33作为干细胞循环肿瘤细胞（stem circulation tumor cell， CTC）捕获探针，发现转移性CRC患者外周血中L33阳性的CTC检出率更高，提示基于L33的CTC捕获分析具有更强的预测转移能力。因此，本研究开发的适体L33可能为转移性CRC的诊断和基于CSC的治疗提供潜在的靶点。

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来源期刊

Bioorganic Chemistry 生物-生化与分子生物学

CiteScore

9.70

自引率

3.90%

发文量

679

审稿时长

31 days

期刊介绍： Bioorganic Chemistry publishes research that addresses biological questions at the molecular level, using organic chemistry and principles of physical organic chemistry. The scope of the journal covers a range of topics at the organic chemistry-biology interface, including: enzyme catalysis, biotransformation and enzyme inhibition; nucleic acids chemistry; medicinal chemistry; natural product chemistry, natural product synthesis and natural product biosynthesis; antimicrobial agents; lipid and peptide chemistry; biophysical chemistry; biological probes; bio-orthogonal chemistry and biomimetic chemistry. For manuscripts dealing with synthetic bioactive compounds, the Journal requires that the molecular target of the compounds described must be known, and must be demonstrated experimentally in the manuscript. For studies involving natural products, if the molecular target is unknown, some data beyond simple cell-based toxicity studies to provide insight into the mechanism of action is required. Studies supported by molecular docking are welcome, but must be supported by experimental data. The Journal does not consider manuscripts that are purely theoretical or computational in nature. The Journal publishes regular articles, short communications and reviews. Reviews are normally invited by Editors or Editorial Board members. Authors of unsolicited reviews should first contact an Editor or Editorial Board member to determine whether the proposed article is within the scope of the Journal.