Peptide nucleic acids targeting oncomiR and tumor-suppressor miRNAs: cancer diagnosis and therapy. Durata: 36 mesi (dal 02/01/2013 al 02/01/2016). Progetto n°: IG13575. Finanziato da: AIRC 2012.

OncomiRNAs and MetastamiRNAs have been described as well as tumor-suppressor microRNAs. With respect to the clinical relevance of microRNA targeting, it is expected that decreased expression of a given miRNA (miRNA interference) is linked with a potential accumulation of targets mRNAs; conversely, increased expression of miRNAs (miRNA replacement) is expected to be causative to low expression of the target mRNAs. In the context of microRNAs and cancer, molecules targeting OncomiRNAs and MetastamiRNAs could represent a strategy to maintain at high levels the mRNA targeted by these tumor-associated miRNAs (often tumor-suppressor mRNAs); mimicking tumor-suppressor miRNAs might lead to a decreased expression of the miRNA mRNA targets (often mRNA coded by oncogenes). In the context of miRNA therapeutics, peptide nucleic acids (PNAs) not only have been demonstrated as molecules exhibiting strong anti-miRNA activity, but also can be designed to mimic miRNA functions when functionalized with cleavage moieties. In respect to therapeutic interventions, PNAs are of great interest, since they are useful regulating gene expression, display high sequence-selectivity and are very stable in biological fluids. The general objectives of the project are: (a) design and validation of PNAs targeting oncomicroRNAs and metastamiRNAs; (b) development and biological validation of novel PNA-based molecules; (c) development of PNAs mimicking the biological activity of tumor-suppressor microRNAs. The results are expected to develop protocols of possible interest for the achievement of very important therapeutic goals for the treatment of cancer.