TY - JOUR
T1 - Axl-Targeted Delivery of the Oncosuppressor miR-137 in Non-small-Cell Lung Cancer
AU - Nuzzo, Silvia
AU - Catuogno, Silvia
AU - Capuozzo, Maria
AU - Fiorelli, Alfonso
AU - Swiderski, Piotr
AU - Boccella, Serena
AU - de Nigris, Filomena
AU - Esposito, Carla Lucia
PY - 2019/9/6
Y1 - 2019/9/6
N2 - 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.
AB - 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.
KW - aptamers
KW - miRNAs
KW - NSCLC
KW - targeted delivery
UR - http://www.scopus.com/inward/record.url?scp=85068119405&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85068119405&partnerID=8YFLogxK
U2 - 10.1016/j.omtn.2019.06.002
DO - 10.1016/j.omtn.2019.06.002
M3 - Article
AN - SCOPUS:85068119405
SN - 2162-2531
VL - 17
SP - 256
EP - 263
JO - Molecular Therapy - Nucleic Acids
JF - Molecular Therapy - Nucleic Acids
ER -