MicroRNAs 221 and 222 in the Pathogenesis of Solid Childhood Tumors

MYCN amplification is a common feature of aggressive neuroblastoma. MicroRNAs (miRNA) are a class of short RNAs that repress translation and promote mRNA degradation by sequence-specific interaction with target mRNAs. Previous studies have associated high expression of the co-regulated miR-221 and miR-222 with progression of various cancer entities. We identified miR-221 to be induced by MYCN in vitro and to correlate with MYCN amplification in primary neuroblastomas. Therefore, we aimed to analyze the effect of manipulating mir221/222-expression in vivo using targeted transgenesis in mice. For this purpose, we developed mice either overexpressing miR-221/222 or deficient in miR-221/222 using knock-out technology. Transgenic mice developing spontaneous tumors including rhabdomyosarcoma, medulloblastoma and soft tissue sarcoma were screened for miR-221 expression. miR-221/222 expression was up-regulated in the tumors compared to the respective control tissues, suggesting an oncogenic role. Crossbreeding the mice overexpressing or lacking miR-221/222 with mice engineered to develop spontaneous embryonal tumors will reveal the contribution of miR-221/222 to tumorigenesis in vivo.