Qiang-Sheng Wang1, Jun Zhou2, Xun Li3. 1. Department of Vasculocardiology, The First Affiliated Hospital of Soochow University, Soochow 215006, PR China. 2. Department of Vasculocardiology, The Affiliated Tongren Hospital of Shanghai Jiaotong University of Medical College, Shanghai 200336, PR China. 3. Department of Vasculocardiology, The First Affiliated Hospital of Soochow University, Soochow 215006, PR China. Electronic address: lixun9798@163.com.
Abstract
BACKGROUND: lncUCA1 is abundantly expressed in the heart, indicating it may be important in maintaining normal myocardial function. However, the underlying mechanism of lncUCA1 in heart disease, particularly myocardial infarction (MI), is still in its infancy. METHODS: LncUCA1 and miR-143 expression were measured in hearts of MI models. Overexpression and knockdown of lncUCA1 in neonatal rat cardiomyocytes were performed to confirm the effects of lncUCA1 in hypoxia-induced apoptosis. RESULTS: The expression of lncUCA1 decreased but miR-143 increased inversely in MI heart. Overexpressing lncUCA1 protected cardiomyocytes from H/R induced apoptosis via inhibiting miR-143, which regulates apoptosis by targeting MDM2/p53 pathway. While silencing lncUCA1 caused miR-143 upregulation and H/R-induced apoptosis increase. Moreover, miR-143 was proved to be a competitive target of lncUCA1. CONCLUSIONS: lncUCA1 might protect cardiomyocyte against H/R induced apoptosis by suppressing miR-143 and modulated the following downstream MDM2/p53 signaling pathway, indicating the therapeutic potential of targeting lncUCA1 for MI.
BACKGROUND:lncUCA1 is abundantly expressed in the heart, indicating it may be important in maintaining normal myocardial function. However, the underlying mechanism of lncUCA1 in heart disease, particularly myocardial infarction (MI), is still in its infancy. METHODS:LncUCA1 and miR-143 expression were measured in hearts of MI models. Overexpression and knockdown of lncUCA1 in neonatal rat cardiomyocytes were performed to confirm the effects of lncUCA1 in hypoxia-induced apoptosis. RESULTS: The expression of lncUCA1 decreased but miR-143 increased inversely in MI heart. Overexpressing lncUCA1 protected cardiomyocytes from H/R induced apoptosis via inhibiting miR-143, which regulates apoptosis by targeting MDM2/p53 pathway. While silencing lncUCA1 caused miR-143 upregulation and H/R-induced apoptosis increase. Moreover, miR-143 was proved to be a competitive target of lncUCA1. CONCLUSIONS:lncUCA1 might protect cardiomyocyte against H/R induced apoptosis by suppressing miR-143 and modulated the following downstream MDM2/p53 signaling pathway, indicating the therapeutic potential of targeting lncUCA1 for MI.
Authors: Clara Apicella; Camino S M Ruano; Sébastien Jacques; Géraldine Gascoin; Céline Méhats; Daniel Vaiman; Francisco Miralles Journal: Front Cell Dev Biol Date: 2021-05-13