Pieter Mestdagh1, Steve Lefever1, Kristina Althoff2, Carina Leonelli1, Jan Hellemans3, Marine Jean-Christophe4, Johannes Schulte2, Jo Vandesompele1
1Center for Medical Genetics, Ghent University, Belgium; 2Department of Pediatric-Oncology, University Hospital Essen, Germany; 3Biogazelle, Ghent, Belgium; 4VIB Laboratory for Molecular Cancer Biology, Leuven, Belgium
Recent studies suggest that our genome is pervasively transcribed and produces many tens of thousands of long non-coding RNAs (lncRNAs). These lncRNAs have been implicated in gene expression regulation through direct interaction with chromatin modifying complexes and their subsequent recruitment to target loci in the genome. To date, only a handful of lncRNAs have been described with dcoumented functions in cancer biology. However, their critical role as regulators of gene expression suggests that lncRNAs, much like microRNAs, might be key components of different cancer pathways.
In order to study lncRNAs in cancer, we designed and extensively validated a high-throughput RT-qPCR lncRNA expression profiling platform capable of quantifying over 1700 lncRNAs in a single run. This platform has been applied to identify lncRNAs downstream of two major cancer genes, MYC and TP53, by means of inducible model systems. Furthermore, we measured lncRNA expression of the entire NCI60 cancer cell line panel.
Both MYC and TP53 were found to directly induce lncRNA expression through direct promoter binding. The findings were validated in primary samples and model systems of different tumour entities. From the NCI60 panel, we identified cancer specific lncRNA signatures, reminiscent of lineage survival oncogene expression patterns. Together, our results suggest that RT-qPCR is a valid screening approach for high-throughput lncRNA quantification revealing multiple candidate cancer lncRNAs.
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