Long Noncoding RNA UCA1 from Hypoxia-Conditioned hMSC-Derived Exosomes Acted as a Novel Exerkine for Cardioprotection Through Targeting miR-873-5p/XIAP Axis

Background: Exosomes (Exo) play important roles in stem cell-induced cardioprotection. Previous study indicated that Exo secreted from hypoxia-conditioned human mesenchymal stem cell (hMSCs) was found to be protective for myocardial injury. The hypothesis of this study is that hypoxia promotes hMSCs to secret lncRNA-UCA1 enriched exosomes, which may play a cardioprotective role in cardiac injury. Methods and Results: In this study, we examined how lncRNA-UCA1 from hMSCs-derived Exo on cardioprotection and its underlying mechanisms. We found that the relative levels of circulating exosomal lncRNA-UCA1 were markedly higher in acute myocardial infarction (AMI) patients than those in healthy volunteers. hMSC-derived exosomes exerted protective effects against cardiomyocyte injury in vitro and in vivo. Hypoxia-conditioned hMSCs-derived exosomes (Hypo-Exo) had an even better performance in cardioprotection than normoxia-conditioned hMSCs-derived exosomes (Nor-Exo). LncRNA-UCA1 was a key component in Hypo-Exo-induced cardioprotection by sponging miR-873-5p. miR-873 enhanced the phosphorylation of AMP-activated protein kinase (AMPK) in cardiomyocytes by targeting X-linked inhibitor of apoptosis protein (XIAP). Conclusion: This study demonstrated that lncRNA-UCA1 from hMSCs-derived Exo played a cardioprotective role through the miR873-5p/XIAP axis and that exosomal lncRNA-UCA1 may be a potential biomarker for AMI diagnosis. Funding Statement: This study was supported by grants from the National Natural Science Foundation of China (Grant No. 81901410, 81871113) and Changzhou Sci & Tech Program. (Grant No.CJ20190102). Declaration of Interests: The authors have declared that no competing interest exists. Ethics Approval Statement: The present study was conducted in accordance with the principles of the Declaration of Helsinki and approved by the Ethics Committee of Changzhou No. 2 People’s Hospital of and the First Affiliated Hospital of Nanjing Medical University. Animal protocols were performed with approval of the Experimental Animals Ethics Committee of the First Affiliated Hospital of Nanjing Medical University (No. IACUC-1905024).