miR-125a-5p inhibits glycolysis by targeting hexokinase-II to improve pulmonary arterial hypertension

Purpose: The aim of this study was to investigate the effect of microRNAs on the proliferation of pulmonary arterial smooth muscle cells (PASMCs) as a result of targeting hexokinase-II (HK-II) and its mechanism of action. Results: Differences in metabolic patterns were found between the normal group and monocrotaline-induced pulmonary arterial hypertension (MCT-PH) group. miR-125a-5p decreased glycolysis levels of monocrotaline (MCT)-induced PASMCs by targeting HK-II and inhibiting its proliferation. In vivo experiments found that miR125a-5p agomir upregulated HK-II expression in the MCT-PH. Right ventricular hypertrophy was reversed and cardiac function improved as a result of decreased mean pulmonary artery pressure (mPAP). Conclusion: In vitro and in vivo experiments both confirmed that miR-125a-5p could inhibit cell glycolysis and PASMC proliferation to improve PAH by targeting HK-II. Methods: HK-II overexpression was constructed, and differentially expressed microRNAs were screened for using microarrays. Serum metabolites were detected using Nuclear Magnetic Resonance (NMR). Through screening for characteristic metabolites in rat body fluids and by analyzing biological functions, disordered metabolic pathways were identified. Activity of the miR-125a-5p target HK-II was measured using a luciferase reporter assay. Expression of downstream molecules was measured by RT-qPCR and/or western blot. Glucose consumption and lactic acid production were analyzed and used as a reflection of glycolysis.