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CircNSD1 promotes cardiac fibrosis through targeting the miR-429-3p/SULF1/Wnt/β-catenin signaling pathway

  
@article{APS11104,
	author = {Dong-ni Ji and Sai-di Jin and Yuan Jiang and Fei-yong Xu and Shu-wei Fan and Yi-lin Zhao and Xin-qi Liu and Hao Sun and Wen-zheng Cheng and Xin-yue Zhang and Xiao-xiang Guan and Bo-wen Zhang and Zhi-min Du and Ying Wang and Ning Wang and Rong Zhang and Ming-yu Zhang and Chao-qian Xu},
	title = {CircNSD1 promotes cardiac fibrosis through targeting the miR-429-3p/SULF1/Wnt/β-catenin signaling pathway},
	journal = {Acta Pharmacologica Sinica},
	volume = {45},
	number = {10},
	year = {2024},
	keywords = {},
	abstract = {Cardiac fibrosis is a detrimental pathological process, which constitutes the key factor for adverse cardiac structural remodeling leading to heart failure and other critical conditions. Circular RNAs (circRNAs) have emerged as important regulators of various cardiovascular diseases. It is known that several circRNAs regulate gene expression and pathological processes by binding miRNAs. In this study we investigated whether a novel circRNA, named circNSD1, and miR-429-3p formed an axis that controls cardiac fibrosis. We established a mouse model of myocardial infarction (MI) for in vivo studies and a cellular model of cardiac fibrogenesis in primary cultured mouse cardiac fibroblasts treated with TGF-β1. We showed that miR-429-3p was markedly downregulated in the cardiac fibrosis models. Through gain- and loss-of-function studies we confirmed miR-429-3p as a negative regulator of cardiac fibrosis. In searching for the upstream regulator of miR-429-3p, we identified circNSD1 that we subsequently demonstrated as an endogenous sponge of miR-429-3p. In MI mice, knockdown of circNSD1 alleviated cardiac fibrosis. Moreover, silence of human circNSD1 suppressed the proliferation and collagen production in human cardiac fibroblasts in vitro. We revealed that circNSD1 directly bound miR-429-3p, thereby upregulating SULF1 expression and activating the Wnt/β-catenin pathway. Collectively, circNSD1 may be a novel target for the treatment of cardiac fibrosis and associated cardiac disease.},
	issn = {1745-7254},	url = {http://www.chinaphar.com/article/view/11104}
}