Key result
In silico analysis identifies circCnot6l and circNtrk3 as novel drivers of hypoxic pulmonary artery remodeling.
Why the study?
The contribution of circular RNAs to pulmonary hypertension pathogenesis remains poorly understood despite emerging evidence of their role in vascular remodelling and inflammation.
In silico analysis of rat transcriptomic datasets identifies circCnot6l and circNtrk3 as promising candidate regulators of hypoxia-induced pulmonary artery remodeling.
Pulmonary hypertension (PH) is a progressive and life-threatening disease characterised by elevated pulmonary arterial pressure, vascular remodelling and right ventricular dysfunction. Emerging evidence implicates circular RNAs (circRNAs) in the regulation of vascular remodelling and inflammation; however, their contribution to PH remains poorly understood. Here, we performed an in silico analysis using a multi-tool circRNA discovery pipeline across three publicly available transcriptomic datasets derived from experimental rat models of PH: H_PRN (PRJNA809145; pulmonary artery tissue from normoxic and hypoxia-induced PH rats; 21% vs. 10% O2; n = 7), H_GSE (GSE159668; right lung tissue from normoxic and hypoxia-induced PH rats; 21% vs. 10% O2; n = 6) and M_PRN (PRJNA732522; total lung tissue from control and monocrotaline-induced PH rats; n = 6). CircRNAs were detected in all datasets; however, robust differentially expressed candidates were identified primarily in the hypoxia-exposed pulmonary artery dataset (H_PRN). In this dataset, three circRNAs—circCnot6l, circSmoc1 and circNtrk3—met the differential expression criteria (Benjamini-Hochberg adjusted p-value (FDR q) < 0.05, absolute log2 fold-change > 1). Downstream network analysis from unpaired samples prioritised circCnot6l and circNtrk3 as potential regulators of circRNA–microRNA (miRNA) and miRNA–messenger RNA axes involving miR-204-5p and miR-205, respectively. The predicted target networks were enriched for genes associated with key PH-related processes, including cell proliferation, adhesion, migration, angiogenesis and vascular development. Collectively, these findings identify circCnot6l and circNtrk3 as promising circRNA candidates involved in hypoxia-induced pulmonary artery remodelling and provide a foundation for future experimental studies investigating circRNA-mediated mechanisms underlying PH pathogenesis.
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Atchison et al. (2026) studied Pulmonary hypertension (n=19). Hypoxia or monocrotaline exposure vs. Normoxia (21% O2) or control was evaluated on Differentially expressed circRNAs. In silico analysis of rat pulmonary hypertension datasets identified circCnot6l and circNtrk3 as candidate circRNAs involved in hypoxia-induced pulmonary artery remodeling.
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