Cerebral cavernous malformations (CCMs) are low-flow vascular malformations in the brain associated with recurrent hemorrhage and seizures. Despite accumulating evidence demonstrating the role of lncRNAs in cerebrovascular disorders, their identification in CCMs pathology remains unknown. The objective of this study was to identify lncRNAs associated with CCMs pathogenesis using CCM patient cohorts. For the first time, researchers profiled long noncoding RNAs in CCMs using whole transcriptome sequencing (RNA-seq) technique. This research is a collaborative effort of researchers from the University of Gothenburg (Prof. Chandrasekhar Kanduri), Gothenburg, Sweden, International Neuroscience Institute, Hannover, Germany (lead by Dr. Souvik Kar) and vascular neurosurgery experts from Germany.
The computational analysis of RNA-seq samples from CCM patients identified 1,967 lncRNAs and 4,928 protein-coding genes (PCGs) to be deregulated in CCMs patients. Among these, some of the deregulated lncRNAs are having a significant correlative expression with more than 100 CCM differentially expressed PCGs. Additionally, gene set enrichment analysis of correlated PCGs revealed critical pathways related to vascular signaling and important biological processes relevant to CCMs pathophysiology. Here, by the transcriptome-wide approach, researchers demonstrate that lncRNAs are prevalent in CCMs disease and are likely to play critical roles in regulating important signaling pathways involved in the disease progression. Detailed future investigations on this set of identified lncRNAs can provide useful insights into biology and, ultimately, contribute to preventing this debilitating disease.
Subhash S, Kalmbach N, Wegner F, et al. Transcriptome-wide Profiling of Cerebral Cavernous Malformations Patients Reveal Important Long noncoding RNA molecular signatures. Sci Rep. 2019;9(1):18203. Published 2019 Dec 3. doi:10.1038/s41598-019-54845-0 [article]