• neural stem cells
• microRNAs
• fate-ambivalent cells
• Drosophila
• brain tumors
• transplant

Primary brain tumors, represents a complex array of cancers classified on the basis of time of onset, anatomical position, histological features, genetic mutations as well as presumed cell types of origin. The most common type of malignant primary brain tumor is glioma. Under the term glioma, are classified types of tumors arising from different glial cells such as astrocytes, oligodendrocytes, microglia and ependymal cells. However, studies in model organisms have shown that glioma can also arise from neural stem cells, progenitors and even neurons. There are several evidences of dysregulation of microRNAs expression in glioma with implication in cancer formation and development. MicroRNAs are small non-coding molecules able to regulate gene expression through inhibition of their target.
Drosophila melanogaster is a good model to study fundamental aspects of neural cell fate regulation and deregulation leading to cancer. In an overexpression screen of 72 microRNAs, I identified four of them able to generate ectopic cells when over-expressed in different types of Drosophila neural lineages. I performed transplant experiments that demonstrated the oncogenic nature of these cells/microRNAs as well as of a few others previously identified in the host laboratory. Immunohistochemistry of ectopic cells generated by microRNA overexpression revealed the co-expression of neural stem cell, neuronal and glial markers in individual cells, a situation never seen in wildtype brains. Presence of such ‘fate-ambivalent’ cells has not yet been detected in mammalian brain cancers and our work prompts enquiry into whether this might occur. Further work may also reveal whether some of the neuro-onco-microRNAs found in our study, or their target genes and pathways, play a conserved role in human cancer.