Effect of a novel regulatory mechanism of the GLI1 oncogene

[Objectives] The Hedgehog (HH) signaling pathway has important roles in tumorigenesis and in the patterning of various tissues during embryonal development. The GLI1 oncogene is one of the key molecules involved in HH signaling and acts as a transcription factor in addition to being a target gene of this pathway. Recent studies showed that GLI1 might be a good therapeutic target for several types of cancer. To identify novel regulatory mechanisms acting on the HH signal transduction pathway, we have focused on post-transcriptional regulation including alternative splicing.[Methods] To find novel post-transcriptional regulation of GLI1, we screened GLI1 sequences from the web-available databases. Putative candidates were verified by using real-time PCR and sequencing. [Results] We found a novel mechanism that has an impact on GLI1 activity, RNA editing. The GLI1 mRNA was highly edited in normal cerebellum but this modification was down-regulated in medulloblastomas. The editing of the GLI1 mRNA changed an amino acid of the GLI1 protein and influenced the GLI1 activity.[Conclusions] Our findings indicate that RNA editing of GLI1 is an important mediator of the HH signaling pathway.The 2nd Japan-China Symposium on Cancer Researc