title: Inhibiting the oncogenic mir-221 by microRNA sponge: toward microRNA-based therapeutics for hepatocellular carcinoma.
abstract: OBJECTIVE
  We evaluated the capability of "microRNA sponges" in sequestering and inhibiting the over-expressed miR-221 in HCC cell lines.
  
  
  BACKGROUND
  Advanced hepatocellular carcinoma (HCC) is a serious public health problem, with no effective cure at present. It has been demonstrated that the deregulation of microRNAs expression contributes to tumorigenesis. In HCC, miR-221 was shown to be up-regulated in more than 70% of the cases and was associated with higher tumor stage, metastasis and a shorter time to recurrence after surgery, suggesting an important pathogenic role. A tumor promoting function of miR-221 was proved in a transgenic mouse model, which was predisposed to the development of liver cancers. These findings suggested that miR-221 could represent a potential target for anti-tumor approaches.
  
  
  METHODS
  Novel adeno and adeno-associated viral vectors (AAVs) were developed: they were genetically modified to drive the expression of multiple binding sites for miR-221, the "miR-221 sponge", which was designed to sequester miR-221 cellular molecules.
  
  
  RESULTS
  Analysis of viral vectors activity in HCC cells revealed their capability to reduce miR-221 endogenous levels, which was accompanied by the increase in CDKN1B/ p27 protein, a known target of miR-221. An increase in apoptosis was also measured in Hep3B cells after infection with any of the two viral vectors in comparison with control vectors, with stronger effects induced by adenovirus compared to AAV vectors.
  
  
  CONCLUSIONS
  The depletion of oncogenic microRNAs represents a potential anti-cancer approach that needs to be tested for safety and efficacy. Here, we describe the development of novel "miR-221 sponge" vectors, which can reduce miR-221 activity in vitro and may be used for in vivo delivery.
authors.affiliation: Department of Molecular Medicine, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran ; Dipartimento di Morfologia, Chirurgia e Medicina Sperimentale, Università di Ferrara, Ferrara, Italy.
authors.forename: Farzaneh
authors.initials: F
authors.lastname: Moshiri
authors.affiliation: Dipartimento di Morfologia, Chirurgia e Medicina Sperimentale, Università di Ferrara, Ferrara, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Callegari
authors.affiliation: Dipartimento di Morfologia, Chirurgia e Medicina Sperimentale, Università di Ferrara, Ferrara, Italy.
authors.forename: Lucilla
authors.initials: L
authors.lastname: D'Abundo
authors.affiliation: Dipartimento di Morfologia, Chirurgia e Medicina Sperimentale, Università di Ferrara, Ferrara, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Corrà
authors.affiliation: Dipartimento di Morfologia, Chirurgia e Medicina Sperimentale, Università di Ferrara, Ferrara, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Lupini
authors.affiliation: Dipartimento di Scienze della Vita e Biotecnologie, Università di Ferrara, Ferrara, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Sabbioni
authors.affiliation: Dipartimento di Morfologia, Chirurgia e Medicina Sperimentale, Università di Ferrara, Ferrara, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Negrini
keywords: Adeno-associated viruses; Adenoviruses; Hepatocellular carcinoma; miR-221; microRNA sponge