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Session 6: Epigenetics Poster 3
Polyarginine peptide nucleic acids inibit biological activity of microRNA 210
Enrica Fabbri 1 , Nicoletta Bianchi 1 , Eleonora Brognara 1 ,Alessia Finotti 1 , Giulia
Breveglieri 1 , Monica Borgatti 1 , Alex Manicardi 2 , Roberto Corradini 2 ,
Rosangela Marchelli 2 and Roberto Gambari 1
1 BioPharmaNet, Department of Biochemistry and Molecular Biology, Ferrara
University, via Fossato di Mortara, 74, 44121, Ferrara, Italy, e-mail:gam@unife.it;
2 Department of Organic Chemistry, Parma University, Parco Area delle Scienze, 17/A,
43124 Parma, Italy.
Peptide nucleic acids are DNA mimics extensively used for pharmacological regulation of
gene expression in antisense and anti-gene therapies. At present, very few data are available
on the use of PNAs as molecules targeting microRNAs. MicroRNAs are a family of small (19
to 25 nucleotide in length) noncoding RNAs that regulate gene expression by sequenceselective
targeting of mRNAs, leading to a translational repression or mRNA degradation,
depending on the degree of complementarity between microRNAs and the target sequences.
MicroRNAs are deeply involved in the control of highly regulated biological functions, such
as differentiation, cell cycle and apoptosis. The aim of the present study was to determine the
activity of a PNA conjugated to polyarginine peptide and designed against microRNA 210, a
microRNA associated to hypoxia and involved in the erythroid differentiation modulation.
Our studies demonstrated that this PNA is efficiently internalized within target cells and
strongly inhibits microRNA 210 activity with an alteration of the raptor and !-globin gene
expression. Unlike commercially available antagomiRs, which need continous
administrations, a single administration of this PNA (without using transfection reagents like
lipofectin or lipofectamine) is sufficient to obtain these biological effects. Our results
demostrate PNA-based molecules are very promising reagents to modulate the biological
activity of micro RNAs.
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