Dataset Information

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

ABSTRACT: 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/?-catenin activation in EH, and suggest that the identified ncRNAs may represent useful biomarkers and therapeutic targets for this condition.

SUBMITTER: Yin L

PROVIDER: S-EPMC7244030 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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

Yin Liang L Yao Jie J Deng Guangxue G Wang Xuemei X Cai Weijuan W Shen Jie J

Aging 20200511 9

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 lnc ...[more]

PMID: 32392180

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Project description:Researchers have been exploring the molecular mechanisms underlying the control of periodontal ligament stem cell (PDLSC) osteogenic differentiation. Recently, long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) were shown to function as competitive endogenous RNAs (ceRNAs) to regulate the effect of microRNAs (miRNAs) on their target genes during cell differentiation. However, comprehensive identification and integrated analysis of lncRNAs and circRNAs acting as ceRNAs during PDLSC osteogenic differentiation have not been performed.PDLSCs were derived from healthy human periodontal ligament and cultured separately with osteogenic induction and normal media for 7 days. Cultured PDLSCs were positive for STRO-1 and CD146 and negative for CD31 and CD45. Osteo-induced PDLSCs showed increased ALP (alkaline phosphatase) activity and up-regulated expression levels of the osteogenesis-related markers ALP, Runt-related transcription factor 2 and osteocalcin. Then, a total of 960 lncRNAs and 1456 circRNAs were found to be differentially expressed by RNA sequencing. The expression profiles of eight lncRNAs and eight circRNAs were measured with quantitative real-time polymerase chain reaction and were shown to agree with the RNA-seq results. Furthermore, the potential functions of lncRNAs and circRNAs as ceRNAs were predicted based on miRanda and were investigated using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis. In total, 147 lncRNAs and 1382 circRNAs were predicted to combine with 148 common miRNAs and compete for miRNA binding sites with 744 messenger RNAs. These mRNAs were predicted to significantly participate in osteoblast differentiation, the MAPK pathway, the Wnt pathway and the signaling pathways regulating pluripotency of stem cells. Among them, lncRNAs coded as TCONS_00212979 and TCONS_00212984, as well as circRNA BANP and circRNA ITCH, might interact with miRNA34a and miRNA146a to regulate PDLSC osteogenic differentiation via the MAPK pathway.This study comprehensively identified lncRNAs/circRNAs and first integrated their potential ceRNA function during PDLSC osteogenic differentiation. These findings suggest that specific lncRNAs and circRNAs might function as ceRNAs to promote PDLSC osteogenic differentiation and periodontal regeneration.

Dataset Information

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

Publications

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

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