Oral 1.04. MicroRNA networks: novel key regulators in thymic epithelial tumors

Thymic epithelial tumors (TET) are the most frequent human primary mediastinal tumors. For invasive and/or relapsing cases no effective treatment regimens have been definied, as relevant pathways are still not known. A biological characterization of the relevant molecules related to the pathogenesis and progression of neoplastic tissue in TET is strongly needed. MicroRNAs (miRNAs) constitute a large group of negative gene regulators playing an important role in carcinogenesis in several tumor systems. Mature miRNAs are single-stranded RNA molecules of 20- to 23-nucleotide (nt) length controlling gene expression in many cellular processes. We recently identified a group of mature miRNAs differentially expressed in tumor versus normal thymic tissues by microarray analysis of 54 formalin-fixed paraffin embedded (FFPE) thymic tumors and 12 normal counterparts. In particular, we found 56 miRNAs that were up-regulated and 31 down-regulated in thymic tumors. We found that a subgroup of these miRNAs was also differentially expressed among the different tumor histotypes. Finally, by bioinformatics analysis we identified molecular pathways whose members are putatively targeted by TET-associated miRNAs and that could impact on TET biology. We performed an Affimetrix-based study on a series of fresh frozen thymoma and normal thymic samples from our series. A deeper characterization of the identified pathways involved in TET carcinogenesis by the identification of the key molecular interactions is in progress. Our preliminary data support a key regulator role of mature miRNA in TET.