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Updated: Apr 2, 2026
A Murine Orthotopic Bladder Tumor Model and Tumor Detection System
Published on: January 12, 2017
Aptamer-Based Discovery of Neuropilin-2 as a Potential Biomarker and Therapeutic Target in Bladder Cancer
Yijun Yuan1, Tiantian Xie1, Xin Hu1
1Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo and Biosensing, Hunan Research Center of the Basic Discipline for Cell Signaling, College of Biology, College of Chemistry and Chemical Engineering, Aptamer Engineering Center of Hunan Province, Hunan University, Changsha, Hunan 410082, China.
Abstract:
Bladder cancer (BLCA) remains a clinically challenging malignancy with high recurrence rates and limited molecular targeting options, highlighting the critical need to identify novel biomarkers and develop targeted molecular tools for improved diagnosis and therapy. Aptamers, owing to their high affinity and specificity, represent promising molecular tools for bladder cancer detection and targeted intervention. Using Cell-SELEX against BLCA SCaBER cells combined with counterselection against normal SV-HUC-1 cells, we successfully obtained a DNA aptamer, ss2, which was subsequently optimized to yield a truncated variant, ss2-2. The resulting aptamer ss2-2 exhibited a strong binding affinity and high specificity for BLCA cells. Through aptamer pull-down coupled to mass spectrometry, the molecular target of ss2-2 was identified as neuropilin-2 (NRP2), a transmembrane glycoprotein. This interaction was further validated through siRNA-mediated knockdown and binding correlation analyses across multiple cell lines. Molecular docking revealed a stable interaction interface between ss2-2 and NRP2. Clinically, immunohistochemistry analysis of a BLCA tissue microarray demonstrated significantly elevated NRP2 expression in BLCA tissues, which correlated with an advanced tumor stage. Functionally, NRP2 knockdown suppressed BLCA cell proliferation, colony formation, and migration and regulated the AMPK, MAPK/ERK, and STAT3 signaling pathways. Collectively, these results identify ss2-2 as a high-affinity aptamer targeting NRP2 and underscore the potential of NRP2 as a promising diagnostic biomarker and therapeutic target in bladder cancer, providing a robust foundation for the development of aptamer-based molecular diagnostic and targeted therapeutic strategies.
Insights
Researchers developed a DNA aptamer, ss2-2, that targets neuropilin-2 (NRP2) on bladder cancer cells. This aptamer shows promise for diagnosing and treating bladder cancer (BLCA) by targeting the elevated NRP2 protein.
Area of Science:
- Biochemistry and Molecular Biology
- Oncology
- Biotechnology
Background:
- Bladder cancer (BLCA) presents significant clinical challenges due to high recurrence rates and limited targeted therapies.
- Novel biomarkers and targeted molecular tools are crucial for advancing BLCA diagnosis and treatment.
- Aptamers offer high affinity and specificity, making them valuable for BLCA detection and intervention.
Purpose of the Study:
- To identify and characterize a novel DNA aptamer for bladder cancer (BLCA) detection and targeted therapy.
- To identify the molecular target of the developed aptamer.
- To evaluate the potential of the target as a diagnostic biomarker and therapeutic target for BLCA.
Main Methods:
- Cell-SELEX (Systematic Evolution of Ligands by Exponential Enrichment) was employed against BLCA cells, with counterselection against normal cells, to isolate aptamers.
- Aptamer pull-down assay coupled with mass spectrometry was used to identify the aptamer's molecular target.
- Immunohistochemistry, siRNA-mediated knockdown, molecular docking, and signaling pathway analysis were performed for validation and functional assessment.
Main Results:
- A high-affinity DNA aptamer, ss2-2, was developed, demonstrating specific binding to BLCA cells.
- The molecular target of ss2-2 was identified as neuropilin-2 (NRP2), a transmembrane glycoprotein.
- Elevated NRP2 expression was observed in BLCA tissues, correlating with advanced tumor stage, and its knockdown suppressed cancer cell proliferation, migration, and altered key signaling pathways.
Conclusions:
- The ss2-2 aptamer is a potent tool for targeting neuropilin-2 (NRP2) in bladder cancer (BLCA).
- Neuropilin-2 (NRP2) shows significant potential as both a diagnostic biomarker and a therapeutic target for BLCA.
- These findings provide a strong basis for developing aptamer-based diagnostic and therapeutic strategies for bladder cancer.
