Drug repurposing in medulloblastoma using integrated functional genomic, epigenomic, and transcriptomic approaches
Although it is now known that miRNAs act in part via post-transcriptional effects on mRNA stability and/or translation to modulate gene expression, other molecular mechanisms by which non-coding RNAs may effect changes in mRNA and protein expression remains poorly elucidated. Specifically, it remains unknown whether miRNAs and LncRNAs, have other post- transcriptional regulatory roles such RNA-editing. The goal of my research project is to utilize a global systems and informatics approach to define the role of ncRNAs in determining molecular phenotypes of embryonal brain tumours. I hypothesize that ncRNAs including miRNAs and LncRNAs, are key regulatory elements that determine tumour disease phenotypes and that miRNAs and LncRNAs act via critical regulatory hubs to effect changes in cellular gene and protein expression patterns. Specifically, I propose to exploit the unique, rich genomic data sets generated by the Huang lab from the studies of primary CNS-PNETs and ATRTs, as well cell lines engineered with differential expression of miRNAs and/or LncRNAs to: Aim 1: Identify key miRNA regulatory hubs that are common across different types of embryonal brain tumours by analyses of matched miRNA and mRNA profiles of 200 embryonal brain tumours. Aim 2: Define the effect of key regulatory miRNA identified in Aim 1 on RNA editing by integrating miRNA expression with RNA isoform patterns from RNAseq data in matched tumour samples. Aim 3: Elucidate the role of novel LncRNAs identified from whole genome sequencing analyses on mRNA expression patterns of CNS-PNETs and ATRTs.
Deena Gendoo , The Hospital For Sick Children
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