LncRNA NEAT1 promotes cardiac hypertrophy through microRNA-19a-3p/SMYD2 axis.

X-L Sun, J-L Lv, L Dou, D Chen, Y-C Zhu, X Hu

European review for medical and pharmacological sciences 2020 Feb

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The role of NEAT1 in cancers has been demonstrated. But the role of NEAT1 in cardiac hypertrophy still remains unknown. This study aimed to elucidate the specific function of long non-coding RNA (lncRNA) NEAT1 in cardiac hypertrophy and its underlying mechanism. In this study, the in vivo and in vitro cardiac hypertrophy models were constructed by transverse aortic coarctation (TAC) procedure in rats and phenylephrine (PE) induction in primary cardiomyocytes, respectively. The expression levels of NEAT1, microRNA-19a-3p, SMYD2, and cardiac hypertrophic markers were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Cardiac hypertrophy was evaluated as calculating the surface area of hypertrophic cardiomyocyte by fluorescein isothiocyanate (FITC)-Phalloidin staining. Luciferase Reporter Gene Assay was conducted to detect the binding of NEAT1, SMYD2, and microRNA-19a-3p. The results showed that NEAT1 and SMYD2 were highly expressed in myocardium of rats with cardiac hypertrophy and PE-induced primary cardiomyocytes, whereas microRNA-19a-3p was lowly expressed. Besides, NEAT1 overexpression markedly upregulated levels of the cardiac hypertrophic markers. Moreover, FITC-Phalloidin staining also revealed hypertrophic cardiomyocytes overexpressing NEAT1. On the contrary, microRNA-19a-3p overexpression reduced the cardiomyocyte surface area and downregulated the levels of the cardiac hypertrophic markers. As luciferase reporter gene assay demonstrated, NEAT1 and SMYD2 could bind to microRNA-19a-3p. Finally, the gain-of-function experiments were designed to verify whether NEAT1 exerted its functions in cardiac hypertrophy by modulating SMYD2 and microRNA-19a-3p. Furthermore, both microRNA-19a-3p overexpression or SMYD2 knockdown could inhibit and reduce the cardiomyocyte surface area, and downregulate the levels of the cardiac hypertrophic markers. In summary, NEAT1 promotes the occurrence and progression of cardiac hypertrophy by upregulating SMYD2 by binding to microRNA-19a-3p.

Citation

X-L Sun, J-L Lv, L Dou, D Chen, Y-C Zhu, X Hu. LncRNA NEAT1 promotes cardiac hypertrophy through microRNA-19a-3p/SMYD2 axis. European review for medical and pharmacological sciences. 2020 Feb;24(3):1367-1377