Russo, Valentina (2016) Innovative therapies based on the use of non-coding RNAs for non-small cell lung cancer (NSCLC). [Tesi di dottorato]
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| Tipologia del documento: | Tesi di dottorato |
|---|---|
| Lingua: | English |
| Titolo: | Innovative therapies based on the use of non-coding RNAs for non-small cell lung cancer (NSCLC) |
| Autori: | Autore Email Russo, Valentina valentina.russo86@alice.it |
| Data: | 31 Marzo 2016 |
| Numero di pagine: | 111 |
| Istituzione: | Università degli Studi di Napoli Federico II |
| Dipartimento: | Medicina Molecolare e Biotecnologie Mediche |
| Scuola di dottorato: | Biotecnologie |
| Dottorato: | Patologia e fisiopatologia molecolare |
| Ciclo di dottorato: | 28 |
| Coordinatore del Corso di dottorato: | nome email Avvedimento, Vittorio Enrico avvedim@unina.it |
| Tutor: | nome email Condorelli, Gerolama [non definito] |
| Data: | 31 Marzo 2016 |
| Numero di pagine: | 111 |
| Parole chiave: | miRNA; aptamer; non-small cell lung cancer; cancer therapy |
| Settori scientifico-disciplinari del MIUR: | Area 05 - Scienze biologiche > BIO/11 - Biologia molecolare Area 06 - Scienze mediche > MED/04 - Patologia generale |
| Depositato il: | 13 Apr 2016 10:35 |
| Ultima modifica: | 05 Mag 2017 01:00 |
| URI: | http://www.fedoa.unina.it/id/eprint/10855 |
Abstract
Recent studies have shown the importance of microRNAs (miRNAs) as key regulators in several human disease, and also their great potential as new class of therapeutics cancer therapeutics. However, a major obstacle to their translation to clinic is actually represented by the lack of a robust and reliable way to selectively deliver them to the target malignant tumor cells. Today, nucleic-acid aptamers represent an expanding new class of biomolecules which is revealing as an interesting and highly promising for the specific delivery of RNA-based therapeutics. In this study, I intend to validate the use of aptamers as cell-specific delivery molecules for “therapeutic” miRNAs. I identified a tumor-suppressive miRNA in non-small cell lung cancer (NSCLC), miR-34c. I demonstrated that the expression of miR-34c is low in NCSCL and when transfected into cell lines is able to impact on cell survival. By applying methods successfully used in our laboratory, I conjugated the tumor-suppressor miR-34c to a nucleic acid aptamer, that selectively recognizes the AXL receptor and is rapidly internalized (GL21.T), generating a “molecular chimera”. With sticky-end annealing, the aptamer and a single chain anti-miRNA (or the passenger strand of the miRNA) are annealed by the mean of complementary sticky ends elongated at the 3’ end of the aptamer and at the 5’ end of the single chain of the miRNA, respectively. I demonstrated that the GL21.T/miR-34c chimera is able to bind and to carry the miRNA within the NSCLC cells. Interestingly, I demonstrated that a miR-34c target is the AXL receptor. Thus, the GL21.T/miR-34c chimera is able to exert a dual inhibition of AXL, either at functional or at transcriptional level. Finally, I evaluated the functional effects of the chimera in NSCLC cells that selectively express AXL receptor.
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