ArticleRespiratory research2023
Circ-Ntrk2 acts as a miR-296-5p sponge to activate the TGF-β1/p38 MAPK pathway and promote pulmonary hypertension and vascular remodelling.
Article in Respiratory research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14 citing papers in PubMed, 22 citations in OpenAlex.
- Integrative gene target mapping, RNA sequencing, in silico molecular docking, ADMET profiling and molecular dynamics simulation study of marine derived molecules for type 1 diabetes mellitus.Molecular diversity · 2026Article
- Circular RNA-mediated regulation of key signaling pathways in cardiovascular diseases: a review.Journal of advanced research · 2026Review
- HO-1-modified umbilical cord MSCs alleviate pulmonary arterial hypertension by reducing inflammation and endothelial dysfunction.Stem cells translational medicine · 2026Article
- Therapeutic Effects of Active Compounds fromACS omega · 2026Article
- LncRNA MEG8 promotes deep vein thrombosis by sponging miR-296-5p to regulate human umbilical vein endothelial cells.Hereditas · 2025Article
- CircRNA-based AntimiR therapy: A novel approach to hypertension treatment.Non-coding RNA research · 2025Review
- Signaling pathways and targeted therapy for pulmonary hypertension.Signal transduction and targeted therapy · 2025Review
- Exploring the Causal Relationship Between Gut Microbiota and Pulmonary Artery Hypertension: Insights From Mendelian Randomization.Journal of the American Heart Association · 2025Article
- Genome-wide characterization of circular RNAs in three rat models of pulmonary hypertension reveals distinct pathological patterns.BMC genomics · 2025Article
- miRNA regulatory networks as precision diagnostic and therapeutic targets in pulmonary arterial hypertension: from molecular cascades to clinical translation.American journal of cardiovascular disease · 2025Review
- The Role of MicroRNAs in the Pathogenesis of Doxorubicin-Induced Vascular Remodeling.International journal of molecular sciences · 2024Review
- Canagliflozin alleviates pulmonary hypertension by activating PPARγ and inhibiting its S225 phosphorylation.Acta pharmacologica Sinica · 2024Article
- CC chemokines Modulate Immune responses in Pulmonary Hypertension.Journal of advanced research · 2024Review
- CircRNA-mediated regulation of cardiovascular disease.Frontiers in cardiovascular medicine · 2024Review
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundCircular RNAs (circRNAs), a novel class of non-coding RNAs, play an important regulatory role in pulmonary arterial hypertension (PAH); however, the specific mechanism is rarely studied. In this study, we aimed to discover functional circRNAs and investigate their effects and mechanisms in hypoxia-induced pulmonary vascular remodelling, a core pathological change in PAH.
methodsRNA sequencing was used to illustrate the expression profile of circRNAs in hypoxic PAH. Bioinformatics, Sanger sequencing, and quantitative real-time PCR were used to identify the ring-forming characteristics of RNA and analyse its expression. Then, we established a hypoxia-induced PAH mouse model to evaluate circRNA function in PAH by echocardiography and hemodynamic measurements. Moreover, microRNA target gene database screening, fluorescence in situ hybridisation, luciferase reporter gene detection, and western blotting were used to explore the mechanism of circRNAs.
resultsRNA sequencing identified 432 differentially expressed circRNAs in mouse hypoxic lung tissues. Our results indicated that circ-Ntrk2 is a stable cytoplasmic circRNA derived from Ntrk2 mRNA and frequently upregulated in hypoxic lung tissue. We further found that circ-Ntrk2 sponges miR-296-5p and miR-296-5p can bind to the 3'-untranslated region of transforming growth factor-β1 (TGF-β1) mRNA, thereby attenuating TGF-β1 translation. Through gene knockout or exogenous expression, we demonstrated that circ-Ntrk2 could promote PAH and vascular remodelling. Moreover, we verified that miR-296-5p overexpression alleviated pulmonary vascular remodelling and improved PAH through the TGF-β1/p38 MAPK pathway.
conclusionsWe identified a new circRNA (circ-Ntrk2) and explored its function and mechanism in PAH, thereby establishing potential targets for the diagnosis and treatment of PAH. Furthermore, our study contributes to the understanding of circRNA in relation to PAH.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.