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Aptamer-miR-34c Conjugate Affects Cell Proliferation of Non-Small-Cell Lung Cancer Cells
- Source :
- Molecular Therapy: Nucleic Acids, Vol 13, Iss, Pp 334-346 (2018), MOLECULAR THERAPY-NUCLEIC ACIDS 13 (2018): 334–346. doi:10.1016/j.omtn.2018.09.016, info:cnr-pdr/source/autori:Russo V.; Paciocco A.; Affinito A.; Roscigno G.; Fiore D.; Palma F.; Galasso M.; Volinia S.; Fiorelli A.; Esposito C.L.; Nuzzo S.; Inghirami G.; de Franciscis V.; Condorelli G./titolo:Aptamer-miR-34c Conjugate Affects Cell Proliferation of Non-Small-Cell Lung Cancer Cells/doi:10.1016%2Fj.omtn.2018.09.016/rivista:MOLECULAR THERAPY-NUCLEIC ACIDS/anno:2018/pagina_da:334/pagina_a:346/intervallo_pagine:334–346/volume:13, Molecular Therapy. Nucleic Acids
- Publication Year :
- 2018
-
Abstract
- MicroRNAs (miRNAs) are key regulators of different human processes that represent a new promising class of cancer therapeutics or therapeutic targets. Indeed, in several tumor types, including non-small-cell lung carcinoma (NSCLC), the deregulated expression of specific miRNAs has been implicated in cell malignancy. As expression levels of the oncosuppressor miR-34c-3p are decreased in NSCLC compared to normal lung, we show that reintroduction of miR-34c-3p reduces NSCLC cell survival in vitro. Further, in order to deliver the miR-34c-based therapeutic selectively to tumor cells, we took advantage of a reported nucleic acid aptamer (GL21.T) that binds and inhibits the AXL transmembrane receptor and is rapidly internalized in the target cells. By applying methods successfully used in our laboratory, we conjugated miR-34c to the GL21.T aptamer as targeting moiety for the selective delivery to AXL-expressing NSCLC cells. We demonstrate that miR-34c-3p and the GL21.T/miR-34c chimera affect NSCLC cell proliferation and are able to overcome acquired RTK-inhibitor resistance by targeting AXL receptor. Thus, the GL21.T/miR-34c chimera exerts dual inhibition of AXL at functional and transcriptional levels and represents a novel therapeutic tool for the treatment of NSCLC. Keywords: miRNA, aptamer, NSCLC, lung cancer, therapeutics
- Subjects :
- 0301 basic medicine
aptamer
lung cancer
miRNA
NSCLC
therapeutics
Aptamer
Article
NO
03 medical and health sciences
Chimera (genetics)
0302 clinical medicine
Drug Discovery
microRNA
Carcinoma
medicine
Receptor
Lung cancer
Cell growth
Chemistry
Drug Discovery3003 Pharmaceutical Science
lcsh:RM1-950
medicine.disease
Transmembrane protein
respiratory tract diseases
therapeutic
lcsh:Therapeutics. Pharmacology
030104 developmental biology
030220 oncology & carcinogenesis
Cancer research
Molecular Medicine
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Molecular Therapy: Nucleic Acids, Vol 13, Iss, Pp 334-346 (2018), MOLECULAR THERAPY-NUCLEIC ACIDS 13 (2018): 334–346. doi:10.1016/j.omtn.2018.09.016, info:cnr-pdr/source/autori:Russo V.; Paciocco A.; Affinito A.; Roscigno G.; Fiore D.; Palma F.; Galasso M.; Volinia S.; Fiorelli A.; Esposito C.L.; Nuzzo S.; Inghirami G.; de Franciscis V.; Condorelli G./titolo:Aptamer-miR-34c Conjugate Affects Cell Proliferation of Non-Small-Cell Lung Cancer Cells/doi:10.1016%2Fj.omtn.2018.09.016/rivista:MOLECULAR THERAPY-NUCLEIC ACIDS/anno:2018/pagina_da:334/pagina_a:346/intervallo_pagine:334–346/volume:13, Molecular Therapy. Nucleic Acids
- Accession number :
- edsair.doi.dedup.....df3ee1b006aae73673cdac3d81d11df9