CRISPR/Cas9 genome editing demonstrates that CCM3 modulates endothelial miRNA expression. CRISPR/Cas9 genome editing demonstrates that CCM3 modulates endothelial miRNA expression

CCM3 regulates blood-brain-barrier integrity and vascular maturation in vivo. CCM3 loss-of-function variants predispose to cerebral cavernous malformations (CCM). Various signalling pathways are deregulated upon CCM3 depletion in endothelial cells (ECs). In this study, we established a crRNA:tracrRNA:Cas9 RNP approach to efficiently knockout CCM3 in human ECs and studied the molecular and functional effects of its long-term inactivation. Using small RNA sequencing, we show that CCM3 regulates the expression of aging‑associated miRNAs. Overall design: Examination of the miRNA expression profile of 4 wild-type CI-huVEC lines and 4 clonal CCM3-knockout CI-huVEC lines