Deregulation of microRNA-31a-5p is involved in the development of primary hypertension by suppressing apoptosis of pulmonary artery smooth muscle cells via targeting TP53

The present study aimed to identify the association between microRNA (miRNA/miR)-31a-5p and the development of hypertension, and its potential molecular mechanism. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analyses were performed to validate the candidate miRNA and genes involved in hypertension, following which an online miRNA database search, luciferase assay, and RT-qPCR and western blot analyses were performed to confirm the interaction between miR-31a-5p and TP53. A MTT assay and flow cytometric analysis were utilized to determine the effect of miR-31a-5p on cell growth and apoptosis. The results revealed that miR-31a-5p and TP53 were the candidate miRNA and gene regulating hypertension, and that TP53 was the virtual target gene of miR-31a-5p with a binding site located in the TP53 3′ untranslated region (3′UTR). It was confirmed by luciferase activity that miR-31a-5p markedly reduced the luciferase activity of the Luc-wild-type-TP53-3′UTR, whereas the mutated putative miR-31a-5p binding located on the TP53-3′UTR was found to eliminate such an inhibitory effect. miR-31a-5p had no effect on specificity protein 1, E2F transcription factor 2 or forkhead box P3 luciferase activity. Smooth muscle cells collected from spontaneously hypertensive rats treated with gold nano-particles containing anti-rno-miR-31a-5p exhibited a lower growth rate and a higher apoptotic rate. The results of the RT-qPCR and western blot analyses showed that miR-31a-5p negatively regulated the expression of TP53, and transfection with the hsa-miR-31a-5p mimic significantly promoted cell growth and inhibited cell apoptosis, whereas transfection with the anti-hsa-miR-31a-5p mimic significantly suppressed cell growth and induced cell apoptosis. Taken together, these findings indicated that miR-31a-5p is involved in hypertension via the accelerated proliferation of arterial smooth muscle cells and inhibition of apoptosis through targeting TP53.