Identification of candidate lncRNAs and circRNAs regulating WNT3/β-catenin signaling in essential hypertension

摘要

Mounting evidence suggests that noncoding RNAs (ncRNAs) contribute to the pathogenesis of cardiovascular diseases. However, their role in essential hypertension (EH) is still unclear. We therefore identified differentially expressed long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) in EH patients from a high-risk population group and constructed a competing endogenous RNA regulatory network that predicts interactions of potential diagnostic and therapeutic relevance between specific lncRNA/circRNA-microRNA-mRNA triplets. Our analysis identified two lncRNAs, transmembrane protein 183A pseudogene (LOC646616) and leucine aminopeptidase 3 pseudogene 2 (LAP3P2), and two circRNAs, hsa_circ_0039388 and hsa_circ_0038648, that are highly co-expressed with both wingless-type MMTV integration site family member 3 (WNT3) and calcium/calmodulin-dependent protein kinase II inhibitor 2 (CAMK2N2) mRNAs and also share common microRNA binding sites with these two transcripts. We also confirmed that a mutually regulated network composed of LOC646616/microRNA-637/WNT3 controls WNT3 expression and influences viability and invasive properties in human arterial smooth muscle cells in vitro. These findings highlight a novel ncRNA-based regulatory mechanism potentially driving WNT/β-catenin activation in EH, and suggest that the identified ncRNAs may represent useful biomarkers and therapeutic targets for this condition.