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Mol Ther Nucleic Acids. 2018 Dec 7;13:334-346. doi: 10.1016/j.omtn.2018.09.016. Epub 2018 Sep 27.

Aptamer-miR-34c Conjugate Affects Cell Proliferation of Non-Small-Cell Lung Cancer Cells.

Author information

1
Department of Molecular Medicine and Medical Biotechnology, "Federico II" University of Naples, Naples, Italy.
2
Department of Molecular Medicine and Medical Biotechnology, "Federico II" University of Naples, Naples, Italy; Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY, USA.
3
Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy.
4
Thoracic Surgery Unit, Università degli Studi della Campania "Luigi Vanvitelli," Naples, Italy.
5
Istituto di Endocrinologia ed Oncologia Sperimentale, Consiglio Nazionale delle Ricerche (CNR), Naples, Italy.
6
IRCCS SDN, Napoli, Italy.
7
Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY, USA.
8
Department of Molecular Medicine and Medical Biotechnology, "Federico II" University of Naples, Naples, Italy; Istituto di Endocrinologia ed Oncologia Sperimentale, Consiglio Nazionale delle Ricerche (CNR), Naples, Italy. Electronic address: gecondor@unina.it.

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:

NSCLC; aptamer; lung cancer; miRNA; therapeutics

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