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Page 18 of 27 J Cancer Metastasis Treat 2019;5:5 I http://dx.doi.org/10.20517/2394-4722.2018.108

Conclusion: BIRC3 mutations identify a very poor prognostic subgroup of patients that fails FCR similar to
patients harboring TP53 abnormalities. If validated, BIRC3 might be used as a new molecular predictor to
select high-risk patients for novel frontline therapeutic approaches. From the biological point of view, BIRC3
mutations enhance the non-canonical NF-κB signaling pathway promoting survival, proliferation and
chemo-refractoriness.

24. Peptide nucleic acid-based targeting of microRNAs: possible therapeutic and diagnostic
applications for glioblastoma

Roberto Gambari

Department of Life Sciences and Biotechnology, Ferrara University, Ferrara 44124, Italy.

Introduction: MicroRNAs (miRNAs) are small noncoding RNAs regulating gene expression by sequence-
selective targeting of mRNAs, leading to translational repression or mRNA degradation. Low miRNA
expression is associated with accumulation of target mRNAs; high miRNA content causes low expression of
target mRNAs. In cancer, microRNAs are associated with tumor onset and progression.

Experimental model: Targeting oncomiRNAs and metastamiRNAs with biomolecules interfering with their
biological activity is of interest and peptide-nucleic acids (PNAs) might be useful. PNAs are DNA analogues in
which the sugar-phosphate backbone has been replaced by N-(2-aminoethyl) glycine units, hybridize to RNA
with high efficiency, are resistant to proteinases and nucleases, and have been proposed as excellent tools for
alteration of gene expression. We have developed novel delivery strategies for PNAs targeting miRNAs, based
on the use of PNAs linked to a poly-arginine R8 peptide tail for efficient cellular delivery. As far as cancer-
related model systems, we focused on PNAs targeting miR-221 and miR-222 in glioblastoma cells.

Results: In a first study, a combined treatment of U251, U373 and T98G glioma cell lines was performed with
different anti-miRNA PNAs (against miR-221, miR-222 and miR-155). Increased pro-apoptotic effects were
obtained with the co-administration of both anti-miR-221 and anti-miR-222 PNAs, or anti-miR-221 and
anti-miR-155 PNAs. In a second study, we demonstrated synergistic effects of co-administration of corilagin
and a PNA targeting miR-221. In a third approach we performed a combined treatment of glioma U251 cells
with the pro-apoptotic pre-miR-124 and the PNA targeting miR-221, showing induction of apoptosis at very
high levels.

Conclusion: PNAs might be a relevant therapeutic tool for anti-cancer miRNA-therapy based on inhibition
of oncomiRNA and metastamiRNAs, as well as mimicking tumor-suppressor miRNAs (funded by AIRC
IG13575 and Horizon 2020 Project ULTRAPLACAD).

25. Liquid biopsy-based colorectal cancer diagnosis: analysis of a limited panel of miRNA in

mice bearing colorectal carcinoma tumor xenografts and in Human plasma samples

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Jessica Gasparello , Matteo Allegretti , Elisa Tremante , Chiara Papi , Enrica Fabbri , Carla
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Azzurra Amoreo , Paolo Romania , Elisa Melucci , Katia Messana , Monica Borgatti , Patrizio
Giacomini , Roberto Gambari , Alessia Finotti 1
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1 Department of Life Sciences and Biotechnology, University of Ferrara, Ferrara 44124, Italy.
2 Oncogenomics and Epigenetics Unit, Regina Elena National Cancer Institute, Rome 00144, Italy.