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Updated: Oct 2, 2025
A Flow Cytometry-Based Cell Surface Protein Binding Assay for Assessing Selectivity and Specificity of an Anticancer Aptamer
Published on: September 13, 2022
A novel DNA aptamer targeting lung cancer stem cells exerts a therapeutic effect by binding and neutralizing Annexin
Yi-Ying Wu1,2, I-Shan Hsieh3, Chia-Hao Tung2
1Clinical Medicine Research Center, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704302, Taiwan.
Abstract:
Cancer remains one of the leading causes of death worldwide. Cancer stem cells (CSCs) are the underlying reason for tumor recurrence, progression, and therapeutic resistance. Aptamers are synthetic single-stranded oligonucleotides that can specifically bind to various molecular targets. Here, we aim to develop an effective aptamer-based biomarker and therapeutic tool that targets CSCs for cancer therapy. We perform whole-cell-based systematic evolution of ligands by exponential enrichment (cell-SELEX) to screen DNA aptamers that specifically bound to lung CSCs, modeled by E-cadherin-silenced A549 cells. We develop a CSC-specific aptamer (AP-9R) specifically recognizing lung CSCs with high affinity and identify Annexin A2, a Ca2+-dependent membrane-binding protein, as its target. Annexin A2 expression was upregulated in lung CSCs and involved in cancer stemness. The expression of Annexin A2 was associated with signatures of stemness and metastasis, as well as poor clinical outcomes, in lung cancer in silico. Moreover, AP-9R decreased Annexin A2 expression and suppressed CSC properties in CSCs in vitro and in vivo. The present findings suggest that Annexin A2 is a CSC marker and regulator, and the CSC-specific aptamer AP-9R has potential theranostic applications for lung cancer.
Insights
Researchers developed a novel aptamer (AP-9R) targeting cancer stem cells (CSCs) by identifying Annexin A2 as a key marker. This aptamer shows potential for lung cancer diagnosis and therapy.
Area of Science:
- Oncology
- Biotechnology
- Molecular Biology
Background:
- Cancer stem cells (CSCs) drive tumor recurrence, metastasis, and treatment resistance.
- Aptamers are synthetic oligonucleotides with high specificity for molecular targets.
- Targeting CSCs is crucial for effective cancer therapy.
Purpose of the Study:
- To develop an aptamer-based biomarker and therapeutic agent targeting lung CSCs.
- To identify specific molecular targets on CSCs for aptamer binding.
- To evaluate the therapeutic potential of the developed aptamer against lung cancer.
Main Methods:
- Whole-cell-based systematic evolution of ligands by exponential enrichment (cell-SELEX) was employed to screen DNA aptamers against lung CSCs.
- Aptamer AP-9R was identified and its target, Annexin A2, was characterized.
- The effect of AP-9R on Annexin A2 expression and CSC properties was assessed in vitro and in vivo.
Main Results:
- Aptamer AP-9R specifically recognized lung CSCs with high affinity.
- Annexin A2 was identified as the target of AP-9R, upregulated in lung CSCs and associated with stemness and poor prognosis.
- AP-9R treatment reduced Annexin A2 expression and suppressed CSC properties in vitro and in vivo.
Conclusions:
- Annexin A2 is a validated CSC marker and regulator in lung cancer.
- The developed CSC-specific aptamer AP-9R demonstrates potential for theranostic applications in lung cancer.
- Targeting Annexin A2 with aptamers offers a promising strategy for overcoming CSC-mediated therapeutic resistance.
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