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A Non-G-Quadruplex DNA Aptamer Targeting NCL for Diagnosis and Therapy in Bladder Cancer
Yunyi Liu1, Bei Hu1, Xiaming Pei2
1State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Biology, Molecular Science and Biomedicine Laboratory and Aptamer Engineering Center of Hunan Province, Hunan University, Changsha, Hunan, 410082, China.
Abstract:
Bladder cancer (BC) is a highly aggressive malignant tumor affecting the urinary system, characterized by metastasis and a poor prognosis that often leads to limited therapeutic success. This study aims to develop a novel DNA aptamer for the diagnosis and treatment of BC using a tissue-based systematic evolution of ligands by an exponential enrichment (SELEX) process. By using SELEX, this work successfully generates a new aptamer named TB-5, which demonstrates a remarkable and specific affinity for nucleolin (NCL) in BC tissues and displays marked biocompatibility both in vitro and in vivo. Additionally, this work shows that NCL is a reliable tissue-specific biomarker in BC. Moreover, according to circular dichroism spectroscopy, TB-5 forms a non-G-quadruplex structure, distinguishing it from the current NCL-targeting aptamer AS1411, and exhibits a distinct binding region on NCL compared to AS1411. Notably, this study further reveals that TB-5 activates NCL function by promoting autophagy and suppressing the migration and invasion of BC cells, which occurs by disrupting mRNA transcription processes. These findings highlight the critical role of NCL in the pathological examination of BC and warrant more comprehensive investigations on anti-NCL aptamers in BC imaging and treatment.
Insights
Researchers developed a novel DNA aptamer, TB-5, for bladder cancer (BC) diagnosis and treatment. This aptamer targets nucleolin (NCL), a key biomarker, showing potential for BC imaging and therapy.
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- Bladder cancer (BC) is an aggressive malignancy with poor prognosis and limited treatment options.
- Nucleolin (NCL) is implicated in BC progression and serves as a potential therapeutic target.
- Novel diagnostic and therapeutic strategies are needed for effective BC management.
Purpose of the Study:
- To develop a novel DNA aptamer for bladder cancer (BC) diagnosis and treatment.
- To investigate the specificity and efficacy of the aptamer against nucleolin (NCL) in BC.
- To explore the therapeutic potential of the aptamer by assessing its effects on BC cell behavior.
Main Methods:
- Systematic Evolution of Ligands by Exponential Enrichment (SELEX) was employed to generate a novel DNA aptamer.
- The aptamer, named TB-5, was characterized for its affinity and specificity towards nucleolin (NCL) in BC tissues.
- Circular dichroism spectroscopy was used to analyze the structural properties of TB-5.
- In vitro and in vivo biocompatibility assays were performed.
- The effects of TB-5 on BC cell autophagy, migration, invasion, and mRNA transcription were evaluated.
Main Results:
- A novel DNA aptamer, TB-5, with high affinity and specificity for nucleolin (NCL) in BC tissues was successfully generated.
- NCL was confirmed as a reliable tissue-specific biomarker for BC.
- TB-5 exhibits a non-G-quadruplex structure and a distinct binding site on NCL compared to the AS1411 aptamer.
- TB-5 demonstrated good biocompatibility in vitro and in vivo.
- TB-5 activated NCL function, promoted autophagy, and suppressed BC cell migration and invasion by disrupting mRNA transcription.
Conclusions:
- The novel DNA aptamer TB-5 shows significant potential for bladder cancer (BC) diagnosis and therapy.
- Nucleolin (NCL) is a validated tissue-specific biomarker for BC, crucial for pathological examination.
- TB-5's unique structure and mechanism of action offer a promising avenue for developing targeted BC treatments and imaging agents.
