The Potential Roles and Applications of the long non-coding RNA- Interactome in glioblastoma Etiology and Treatment

Long non-coding RNAs (lncRNAs) are a heterogenous population of largely evolutionary preserved transcripts, over 200nt in length which play important roles in human health and disease. These versatile and numerous transcripts can possess RNA:Protein, RNA:RNA, and RNA:DNA binding potential. Some lncRNAs also encode short peptides which can have biological significance. Many, if not a plurality of known lncRNAs, are expressed in the brain, believed to help encode complex information and facilitate various neurologic processes. In fact, lncRNA expression appears to be positively correlated with organism and organ complexity in stark contrast to coding genes. Glioblastoma (GBM) is the most common primary brain tumor with a dismal prognosis. The 5-year survival rate for GBM is around 7% with a median survival of between 14-16mos. GBM standard of care has not changed much in past decades and there is a need for new therapeutic strategies. In this review we focus on six lncRNAs of significance to cancer highlighting their potential applications in GBM treatment. These lncRNAs are MALAT1/NEAT2, HOTAIR, ZFAS1, SOX2-OT, CASC19/PCAT2, and SAMMSON. Some of these lncRNAs are well characterized across numerous cancers, but most are poorly characterized in the context of GBM or glioma. Many lncRNAs, including those highlighted herein, have been implicated in therapy resistance including chemoresistance and radiation resistance. Some of these transcripts can be found in patient serum. lncRNAs then present potential as theragnostic, prognostic, and diagnostic potential for GBM and other cancers. They may also represent therapeutic opportunities directly and as concomitant therapies to address resistance mechanisms.