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4. MicroRNAs miR-584-5p and miR-425-3p Are Up-Regulated in Plasma of Colorectal Cancer (CRC) Patients: Targeting with Inhibitor Peptide Nucleic Acids Is Associated with Induction of Apoptosis in Colon Cancer Cell Lines

Author

Gasparello, Jessica, primary, Papi, Chiara, additional, Zurlo, Matteo, additional, Gambari, Laura, additional, Manicardi, Alex, additional, Rozzi, Andrea, additional, Ferrarini, Matteo, additional, Corradini, Roberto, additional, Gambari, Roberto, additional, and Finotti, Alessia, additional

Published
2022
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6. MicroRNAs miR-584-5p and miR-425-3p Are Up-Regulated in Plasma of Colorectal Cancer (CRC) Patients: Targeting with Inhibitor Peptide Nucleic Acids Is Associated with Induction of Apoptosis in Colon Cancer Cell Lines.

Author

Gasparello, Jessica, Papi, Chiara, Zurlo, Matteo, Gambari, Laura, Manicardi, Alex, Rozzi, Andrea, Ferrarini, Matteo, Corradini, Roberto, Gambari, Roberto, and Finotti, Alessia

Subjects
FUNCTIONAL foods, BIOPSY, SEQUENCE analysis, MICRORNA, APOPTOSIS, ANTINEOPLASTIC agents, COLORECTAL cancer, CELLULAR signal transduction, CELL lines, NUCLEIC acids
Abstract

Simple Summary: Starting from a list of nine miRNAs found to be dysregulated in the bloodstream of early-stage colon cancer (CRC) patients, the biological effects of the targeting of the most relevant up-regulated miRNAs with anti-miRNA peptide nucleic acids (PNAs) were verified. The down-regulation of these target miRNAs with PNAs is associated with apoptosis induction in CRC cellular models. Apoptosis induction, which is one of the most important anticancer mechanisms, reaches very high levels when anti-miRNAs PNAs are combined with other pro-apoptotic compounds such as sulforaphane. Liquid biopsy has dramatically changed cancer management in the last decade; however, despite the huge number of miRNA signatures available for diagnostic or prognostic purposes, it is still unclear if dysregulated miRNAs in the bloodstream could be used to develop miRNA-based therapeutic approaches. In one author's previous work, nine miRNAs were found to be dysregulated in early-stage colon cancer (CRC) patients by NGS analysis followed by RT-dd-PCR validation. In the present study, the biological effects of the targeting of the most relevant dysregulated miRNAs with anti-miRNA peptide nucleic acids (PNAs) were verified, and their anticancer activity in terms of apoptosis induction was evaluated. Our data demonstrate that targeting bloodstream up-regulated miRNAs using anti-miRNA PNAs leads to the down-regulation of target miRNAs associated with inhibition of the activation of the pro-apoptotic pathway in CRC cellular models. Moreover, very high percentages of apoptotic cells were found when the anti-miRNA PNAs were associated with other pro-apoptotic agents, such as sulforaphane (SFN). The presented data sustain the idea that the targeting of miRNAs up-regulated in the bloodstream with a known role in tumor pathology might be a tool for the design of protocols for anti-tumor therapy based on miRNA-targeting molecules. [ABSTRACT FROM AUTHOR]

Published
2023
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16. A Peptide Nucleic Acid (PNA) Masking the miR-145-5p Binding Site of the 3′UTR of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) mRNA Enhances CFTR Expression in Calu-3 Cells

Author

Sultan, Shaiq, primary, Rozzi, Andrea, additional, Gasparello, Jessica, additional, Manicardi, Alex, additional, Corradini, Roberto, additional, Papi, Chiara, additional, Finotti, Alessia, additional, Lampronti, Ilaria, additional, Reali, Eva, additional, Cabrini, Giulio, additional, Gambari, Roberto, additional, and Borgatti, Monica, additional

Published
2020
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19. Sistemi sensoristici avanzati basati su PNA

Author

Rozzi, Andrea

Subjects
genosensing, Non compilare, CHIM/06, advanced sensor, PNA, modified-PNA
Abstract

In questa tesi di dottorato sono descritte le premesse teoriche, le procedure sperimentali e le conclusioni riguardanti lo sviluppo di diversi sistemi sensoristici avanzati, principalmente basti su acidi peptido nucleici (PNA). Questi analoghi sintetici del DNA sono stati usati per lo sviluppo di diversi geno-sensori, con trasduzione ottica o elettronica. In particolare la tesi, dopo due capitoli introduttivi sulle moderne tecniche sensoristiche e sulla sintesi di PNA presenta la sintesi di PNA modificati per sonde molecolari fluorescenti, la sintesi di PNA modificati e non per la rivelazione precoce del cancro al colon-retto, sintesi di PNA per la rivelazione di DNA genomico della soia transgenica, sviluppo di nuove piattaforme utilizzando PNA e biotina come sonde di cattura. In this Doctoral Thesis, there will be described theoretical knowledge, experimental procedure and conclusion regarding the development of different advanced sensory systems, mainly based on peptide nucleic acids (PNA). These synthetic analogous of DNA have been used for the development of different kinds of genosensor, with optics or electronics transduction. In particular, after two introducing chapter on newly DNA-sensing techniques and PNA synthesis the thesis focus on synthesis of modified-PNA for fluorescent molecular probes, synthesis of modified and unmodified PNAs for early colorectal cancer diagnosis, synthesis of PNA for detection of genomic transgenic soy DNA, development of new sensing platform exploiting PNA and biotin as capture probes.

Published
2019

24. A Bifunctional Monomer for On-Resin Synthesis of Polyfunctional PNAs and Tailored Induced-Fit Switching Probes

Author

Manicardi, Alex, Bertucci, Alessandro, Rozzi, Andrea, and Corradini, Roberto

Subjects
Peptide nucleic acid, 010405 organic chemistry, Oligonucleotide, Stereochemistry, Organic Chemistry, Substituent, 010402 general chemistry, 01 natural sciences, Biochemistry, Combinatorial chemistry, 0104 chemical sciences, Nucleobase, chemistry.chemical_compound, Monomer, chemistry, Molecular beacon, Pyrene, Physical and Theoretical Chemistry, Bifunctional
Abstract

A synthetic strategy for the production of polyfunctional PNAs bearing substituent groups both on the nucleobase and on the backbone C5 carbon of the same monomer is described; this is based on the use of a tris-orthogonally protected monomer and subsequent solid-phase selective functionalization. This strategy can be used for synthesizing PNAs that are not readily accessible by use of preformed modified monomers. As an example, a PNA-based probe that undergoes a switch in its fluorescence emission upon hybridization with a target oligonucleotide, induced by tailor-made movement of two pyrene substituent groups, was synthesized.

Published
2016

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