Axl-Targeted Delivery of the Oncosuppressor miR-137 in Non-small-Cell Lung Cancer
Non-small-cell lung cancer (NSCLC) accounts for 85%–90% of all cases of lung cancer that is the most deadly type of cancer. Despite advances in chemotherapy and radiotherapy, severe side effects and frequent drug resistance limit the success of the treatments, and the identification of new therapeut...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2019-09-01
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| Series: | Molecular Therapy: Nucleic Acids |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2162253119301635 |
| _version_ | 1818048766930845696 |
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| author | Silvia Nuzzo Silvia Catuogno Maria Capuozzo Alfonso Fiorelli Piotr Swiderski Serena Boccella Filomena de Nigris Carla Lucia Esposito |
| author_facet | Silvia Nuzzo Silvia Catuogno Maria Capuozzo Alfonso Fiorelli Piotr Swiderski Serena Boccella Filomena de Nigris Carla Lucia Esposito |
| author_sort | Silvia Nuzzo |
| collection | DOAJ |
| description | Non-small-cell lung cancer (NSCLC) accounts for 85%–90% of all cases of lung cancer that is the most deadly type of cancer. Despite advances in chemotherapy and radiotherapy, severe side effects and frequent drug resistance limit the success of the treatments, and the identification of new therapeutic options still represents a crucial challenge. Here, we provide the evidence for the therapeutic potential of an aptamer-microRNA (miR) complex (AmiC) composed by an aptamer (GL21.T), able to bind and antagonize the oncogenic receptor Axl, and the miR-137, downregulated in lung cancer and involved in cell survival and proliferation. We found that, when applied to Axl-expressing NSCLC cancer cells, the complex is effectively internalized, increasing miR cellular levels and downregulating miR targets. Most importantly, the complex combines the inhibitory function of the GL21.T aptamer and miR-137, leading to a negative impact on NSCLC migration and growth. The described AmiC thus represents a promising tool for the development of new therapeutic approaches for NSCLC. Keywords: aptamers, miRNAs, NSCLC, targeted delivery |
| first_indexed | 2024-12-10T10:26:54Z |
| format | Article |
| id | doaj.art-a85c657154e04d3d8811c3e693d25318 |
| institution | Directory Open Access Journal |
| issn | 2162-2531 |
| language | English |
| last_indexed | 2024-12-10T10:26:54Z |
| publishDate | 2019-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Nucleic Acids |
| spelling | doaj.art-a85c657154e04d3d8811c3e693d253182022-12-22T01:52:41ZengElsevierMolecular Therapy: Nucleic Acids2162-25312019-09-0117256263Axl-Targeted Delivery of the Oncosuppressor miR-137 in Non-small-Cell Lung CancerSilvia Nuzzo0Silvia Catuogno1Maria Capuozzo2Alfonso Fiorelli3Piotr Swiderski4Serena Boccella5Filomena de Nigris6Carla Lucia Esposito7IRCCS SDN, Naples, ItalyIstituto di Endocrinologia ed Oncologia Sperimentale, Consiglio Nazionale delle Ricerche (CNR), Naples, ItalyIstituto di Endocrinologia ed Oncologia Sperimentale, Consiglio Nazionale delle Ricerche (CNR), Naples, ItalyThoracic Surgery Unit, University of Campania “Luigi Vanvitelli,” Naples, ItalyDNA/RNA Synthesis Laboratory, Beckman Research Institute of City the of Hope, Duarte, CA, USADepartment of Experimental Medicine, University of Campania “Luigi Vanvitelli,” Naples, ItalyDepartment of Precision Medicine, University of Campania “Luigi Vanvitelli,” Naples, Italy; Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, College of Science and Technology, Temple University, Philadelphia, PA, USAIstituto di Endocrinologia ed Oncologia Sperimentale, Consiglio Nazionale delle Ricerche (CNR), Naples, Italy; Corresponding author: Carla Lucia Esposito, Istituto di Endocrinologia ed Oncologia Sperimentale, Consiglio Nazionale delle Ricerche (CNR), Via T. de Amicis, 80131 Naples, Italy.Non-small-cell lung cancer (NSCLC) accounts for 85%–90% of all cases of lung cancer that is the most deadly type of cancer. Despite advances in chemotherapy and radiotherapy, severe side effects and frequent drug resistance limit the success of the treatments, and the identification of new therapeutic options still represents a crucial challenge. Here, we provide the evidence for the therapeutic potential of an aptamer-microRNA (miR) complex (AmiC) composed by an aptamer (GL21.T), able to bind and antagonize the oncogenic receptor Axl, and the miR-137, downregulated in lung cancer and involved in cell survival and proliferation. We found that, when applied to Axl-expressing NSCLC cancer cells, the complex is effectively internalized, increasing miR cellular levels and downregulating miR targets. Most importantly, the complex combines the inhibitory function of the GL21.T aptamer and miR-137, leading to a negative impact on NSCLC migration and growth. The described AmiC thus represents a promising tool for the development of new therapeutic approaches for NSCLC. Keywords: aptamers, miRNAs, NSCLC, targeted deliveryhttp://www.sciencedirect.com/science/article/pii/S2162253119301635 |
| spellingShingle | Silvia Nuzzo Silvia Catuogno Maria Capuozzo Alfonso Fiorelli Piotr Swiderski Serena Boccella Filomena de Nigris Carla Lucia Esposito Axl-Targeted Delivery of the Oncosuppressor miR-137 in Non-small-Cell Lung Cancer Molecular Therapy: Nucleic Acids |
| title | Axl-Targeted Delivery of the Oncosuppressor miR-137 in Non-small-Cell Lung Cancer |
| title_full | Axl-Targeted Delivery of the Oncosuppressor miR-137 in Non-small-Cell Lung Cancer |
| title_fullStr | Axl-Targeted Delivery of the Oncosuppressor miR-137 in Non-small-Cell Lung Cancer |
| title_full_unstemmed | Axl-Targeted Delivery of the Oncosuppressor miR-137 in Non-small-Cell Lung Cancer |
| title_short | Axl-Targeted Delivery of the Oncosuppressor miR-137 in Non-small-Cell Lung Cancer |
| title_sort | axl targeted delivery of the oncosuppressor mir 137 in non small cell lung cancer |
| url | http://www.sciencedirect.com/science/article/pii/S2162253119301635 |
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