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

Valentina Russo, Alessia Paciocco, Alessandra Affinito, Giuseppina Roscigno, Danilo Fiore, Francesco Palma, Marco Galasso, Stefano Volinia, Alfonso Fiorelli, Carla Lucia Esposito, Silvia Nuzzo, Giorgio Inghirami, Vittorio de Franciscis, Gerolama Condorelli

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)334-346
Number of pages13
JournalMolecular Therapy - Nucleic Acids
Volume13
DOIs
Publication statusPublished - Dec 7 2018

Keywords

  • aptamer
  • lung cancer
  • miRNA
  • NSCLC
  • therapeutics

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

Fingerprint Dive into the research topics of 'Aptamer-miR-34c Conjugate Affects Cell Proliferation of Non-Small-Cell Lung Cancer Cells'. Together they form a unique fingerprint.

Cite this