GENO-04REGULATION OF GLIOBLASTOMA BY NOVEL LONG NONCODING RNA (lncRNA)

Abstract

The human genome produces many thousands of long noncoding RNAs (lncRNAs) – transcripts >200 nucleotides long with little evidence of protein coding potential. It is now clear that lncRNAs can have critical biological functions and roles in human disease including cancer. Because lncRNAs are particularly cell and disease specific, they are attractive as therapeutic targets. However, very few specific lncRNAs have been identified as potential targets for cancer therapy. We have recently identifiedPinky (Pnky) as a novel lncRNA that regulates the production of neurons from neural stem cells (NSCs) in the embryonic and adult brain (Ramos et al., Cell Stem Cell 2013; Ramos et al., Cell Stem Cell 2015). Pnky-deficiency in NSCs increased neuronal differentiation, depleting the NSC population. Moreover, human GBM tumors expressed the human PNKY transcript, and single cell RNA-seq data analysis indicated that PNKYis present in a specific subset of individual GBM tumor cells. In the Ink/Arf-null, EGFRvIII mouse glioma model, Pnky was also found to be highly expressed, and ongoing studies indicate a function for Pnky in this brain tumor model. Upcoming results may reveal the critical importance of Pnky and other specific lncRNAs in the proliferation of GBM. Overall, our work lays important groundwork for the development of lncRNAs as a large new class of therapeutic targets for the treatment of gliomas.