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Abstract Background Hypertension is a main contributing factor of cardiovascular diseases; deregulated circular RNAs are involved in the pathogenesis of pulmonary arterial hypertension (PAH). Herein, we evaluated the function and mechanism of circST6GAL1 in PAH process. Methods Human pulmonary artery smooth muscle cells (HPASMCs) were cultured in hypoxic environment for functional analysis. The cell counting kit‐8, 5‐ethynyl‐2′‐deoxyuridine, wound healing, and flow cytometry assays were used to investigate cell proliferation, migration, and apoptosis. qRT‐PCR and Western blotting analyses were used for level measurement of genes and proteins. The binding between miR‐509‐5p and circST6GAL1 or multiple C2 and transmembrane domain containing 2 (MCTP2) was analyzed by dual‐luciferase reporter, RNA immunoprecipitation, and pull‐down assays. The monocrotaline (MCT)‐induced PAH mouse models were established for in vivo assay. Results CircST6GAL1 was highly expressed in PAH patients and hypoxia‐induced HPASMCs. Functionally, circST6GAL1 deficiency reversed hypoxia‐induced proliferation and migration, as well as apoptosis arrest in HPASMCs. Mechanistically, circST6GAL1 directly targeted miR‐509‐5p, and MCTP2 was a target of miR‐509‐5p. Rescue assays showed that the regulatory effects of circST6GAL1 deficiency on hypoxia‐induced HPASMCs were abolished. Moreover, forced expression of miR‐509‐5p suppressed HPASMC proliferation and migration and induced cell apoptosis under hypoxia stimulation, while these effects were abolished by MCTP2 overexpression. Moreover, circST6GAL1 silencing improved MCT‐induced pulmonary vascular remodeling and PAH. Conclusion CircST6GAL1 deficiency reversed hypoxia‐induced proliferation and migration, as well as apoptosis arrest in HPASMCs, and alleviated pulmonary vascular remodeling in MCT‐induced PAH mouse models through the miR‐509‐5p/MCTP2 axis, indicating a potential therapeutic target for PAH.

Abstract Here, a sucrose non‐fermenting‐1‐related protein kinase alpha subunit (TaSnRK1α‐1A) is identified as associated with cold stress through integration of genome‐wide association study, bulked segregant RNA sequencing, and virus‐induced gene silencing. It is confirmed that TaSnRK1α positively regulates cold tolerance by transgenes and ethyl methanesulfonate (EMS) mutants. A plastid‐lipid‐associated protein 6, chloroplastic‐like (TaPAP6L‐2B) strongly interacting with TaSnRK1α‐1A is screened. Molecular chaperone DJ‐1 family protein (TaDJ‐1‐7B) possibly bridged the interaction of TaSnRK1α‐1A and TaPAP6L‐2B. It is further revealed that TaSnRK1α‐1A phosphorylated TaPAP6L‐2B. Subsequently, a superior haplotype TaPAP6L‐2B30S/38S is identified and confirmed that both R30S and G38S are important phosphorylation sites that influence TaPAP6L‐2B in cold tolerance. Overexpression (OE) and EMS‐mutant lines verified TaPAP6L positively modulating cold tolerance. Furthermore, transcriptome sequencing revealed that TaPAP6L‐2B‐OE lines significantly increased jasmonic acid (JA) content, possibly by improving precursor α‐linolenic acid contributing to JA synthesis and by repressing JAR1 degrading JA. Exogenous JA significantly improved the cold tolerance of wheat plants. In summary, TaSnRK1α profoundly regulated cold stress, possibly through phosphorylating TaPAP6L to increase endogenous JA content of wheat plants.