Effect of a novel regulatory mechanism of the GLI1 oncogene in medulloblasto

The Hedgehog (HH) signaling pathway has important role in tumorigenesis and in patterning various tissues during embryonal development. GLI1 oncogene is one of the key molecules involved in the HH signaling pathway and acts as a transcription factor in addition to being a target gene of the pathway. Recent studies showed GLI1 might be a good therapeutic target for several type of cancer. To identify novel regulatory mechanisms acting on the HH signal transduction pathway, we have focused on post-transcriptional regulation including alternative splicing. In this presentation, we demonstrate a novel mechanism of GLI1 activity by RNA editing. GLI1 mRNA was highly edited in normal cerebellum but the modification was down-regulated in medulloblastoma. This editing of GLI1 mRNA change an amino acid of GLI1 protein and influenced GLI1 activity. In conclusion, our findings indicate the RNA editing of GLI1 is an important mediator of the HH signaling pathway.70th Annual Meeting of the Japanese Cancer Association (JCA