Circ_nuclear factor I X (circNfix) attenuates pressure overload-induced cardiac hypertrophy via regulating miR-145-5p/ATF3 axis

Abstract

Cardiac hypertrophy can cause heart failure. However, the mechanisms underlying the progression of cardiac hypertrophy remain unclear. Emerging evidence suggests that circular RNAs (circRNAs) play a critical role in cardiac hypertrophy. However, the association between circ_nuclear factor I X (circNfix) and cardiac hypertrophy remain largely unknown. Therefore, the aim of the present study was to explore the role of circNfix in cardiac hypertrophy. In order to detect the function of circNfix in cardiac hypertrophy, cardiomyocytes were stimulated with angiotensin II (Ang II) to mimic the pathogenesis of the disease. In addition, pressure overload-induced cardiac hypertrophy in a mouse model was established using transverse aortic constriction (TAC) surgery. The mechanism via which circNfix regulated cardiac hypertrophy was investigated using RNA pulldown and luciferase reporter assays, and fluorescence in situ hybridization (FISH). circNfix was downregulated in Ang II-treated cardiomyocytes. Similarly, circNfix expression was markedly downregulated in mice following TAC surgery. In addition, circNfix overexpression significantly prevented the progression of cardiac hypertrophy in TAC-treated mice. Luciferase activity and RNA pull-down assays indicated that circNfix could indirectly target activating transcription factor 3 (ATF3) by binding with microRNA (miR)-145-5p in cardiomyocytes. miR-145-5p overexpression or ATF3 knockdown could reverse the effects of circNfix in Ang II-treated mouse cardiomyocytes. circNfix attenuated pressure overload-induced cardiac hypertrophy by regulating the miR-145-5p/ ATF3 axis. Therefore, circNfix may serve as a molecular target for cardiac hypertrophy treatment.

Tripartite motif 27 promotes cardiac hypertrophy via PTEN/Akt/mTOR signal pathways

“…The blood vessel and the needle were ligated together, and then the needle was removed to achieve the corresponding degree of blood vessel constriction. After the ligation was completed, sutures were sequentially completed [ 23 ]. After the arterial arch ligation, once the mouse has spontaneous breathing and a strong response to the pinch, the tracheal intubation was pulled out, and the mouse was placed in a cage containing autoclaved bedding, feed, and drinking water.…”

Non-Coding RNAs in the Therapeutic Landscape of Pathological Cardiac Hypertrophy

“…Recent work showed that miR-145-5p worsens pathological response in AngII-treated cardiomyocytes, by decreasing the expression of activating transcription factor 3 (ATF3). ATF3 is part of the cAMP response element-binding protein/ATF family, and its expression has shown protective effects in hypertensive hearts [ 41 , 42 ]. In this study, inhibition of this miRNA showed restoration of ATF3 levels and consequent attenuation of pressure overload-induced hypertrophy [ 41 ].…”

“…ATF3 is part of the cAMP response element-binding protein/ATF family, and its expression has shown protective effects in hypertensive hearts [ 41 , 42 ]. In this study, inhibition of this miRNA showed restoration of ATF3 levels and consequent attenuation of pressure overload-induced hypertrophy [ 41 ]. Interestingly, circ_nuclear factor I X (circNfix), reportedly, sponged miR-145-5p and abolished its detrimental effect on inhibiting ATF3 expression.…”

“…Interestingly, circ_nuclear factor I X (circNfix), reportedly, sponged miR-145-5p and abolished its detrimental effect on inhibiting ATF3 expression. Overexpression of this circRNA reversed cardiac hypertrophy in mice subjected to TAC [ 41 ].…”

MiR-410-3p facilitates Angiotensin II–induced cardiac hypertrophy by targeting Smad7

“…MicroRNAs have drawn more and more attention in cardiovascular research field [ 6 , 7 ]. Indeed, mounting evidence shows that this 21~25 nt long oligonucleotide are critically involved in regulation of a series of biological processes in cardiovascular system, such as physiological and/or pathological cardiac hypertrophy, cell apoptosis, autophagy, cardiac inflammatory response, and remodeling [ 8–14 ].…”