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Potential Therapeutic Use of Aptamers against HAT1 in Lung Cancer
José Ignacio Klett-Mingo1, Celia Pinto-Díez2, Julio Cambronero-Plaza1
1Grupo de Aptámeros, Departamento de Bioquímica-Investigación, IRYCIS-Hospital Universitario Ramón y Cajal, Carretera de Colmenar Viejo Km. 9.100, 28034 Madrid, Spain.
Abstract:
Lung cancer is one of the leading causes of death worldwide and the most common of all cancer types. Histone acetyltransferase 1 (HAT1) has attracted increasing interest as a potential therapeutic target due to its involvement in multiple pathologies, including cancer. Aptamers are single-stranded RNA or DNA molecules whose three-dimensional structure allows them to bind to a target molecule with high specificity and affinity, thus making them exceptional candidates for use as diagnostic or therapeutic tools. In this work, aptamers against HAT1 were obtained, subsequently characterized, and optimized, showing high affinity and specificity for HAT1 and the ability to inhibit acetyltransferase activity in vitro. Of those tested, the apHAT610 aptamer reduced cell viability, induced apoptosis and cell cycle arrest, and inhibited colony formation in lung cancer cell lines. All these results indicate that the apHAT610 aptamer is a potential drug for the treatment of lung cancer.
Insights
A novel aptamer, apHAT610, targets Histone acetyltransferase 1 (HAT1) to combat lung cancer. This aptamer effectively reduced cancer cell viability and induced apoptosis, showing promise as a new lung cancer therapeutic.
Area of Science:
- Oncology
- Molecular Biology
- Biotechnology
Background:
- Lung cancer is a leading global cause of mortality and the most prevalent cancer type.
- Histone acetyltransferase 1 (HAT1) is implicated in various diseases, including cancer, making it a potential therapeutic target.
- Aptamers, with their high specificity and affinity, are promising for diagnostic and therapeutic applications.
Purpose of the Study:
- To develop and characterize aptamers targeting Histone acetyltransferase 1 (HAT1).
- To evaluate the therapeutic potential of a specific HAT1-targeting aptamer (apHAT610) against lung cancer cell lines.
Main Methods:
- Selection and characterization of aptamers against HAT1.
- In vitro assessment of aptamer binding affinity and specificity.
- Evaluation of apHAT610's effect on lung cancer cell viability, apoptosis, cell cycle, and colony formation.
Main Results:
- Aptamers with high affinity and specificity for HAT1 were successfully generated.
- The apHAT610 aptamer demonstrated the ability to inhibit HAT1 acetyltransferase activity in vitro.
- apHAT610 significantly reduced lung cancer cell viability, induced apoptosis, caused cell cycle arrest, and inhibited colony formation.
Conclusions:
- The apHAT610 aptamer exhibits potent anti-lung cancer activity.
- apHAT610 represents a promising novel therapeutic candidate for lung cancer treatment.
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