LncRNA-NEAT1 from the competing endogenous RNA network promotes cardioprotective efficacy of mesenchymal stem cell-derived exosomes induced by macrophage migration inhibitory factor via the miR-142-3p/FOXO1 signaling pathway

Abstract

Aims: Extracellular vesicles, especially exosomes, have emerged as key mediators of intercellular communication with the potential to improve cardiac function as part of cell-based therapies. We previously demonstrated that the cardioprotective factor, macrophage migration inhibitory factor (MIF), had an optimizing effect on mesenchymal stem cells (MSCs). The aim of this study was to determine the protective function of exosomes derived from MIFpretreated MSCs in cardiomyocytes and to explore the underlying mechanisms. Methods and results: Exosomes were isolated from control MSCs (exosome) and MIF-pretreated MSCs (exosome MIF), and delivered to cardiomyocytes subjected to H 2 O 2 in vitro. Regulatory long non-coding RNAs (lncRNAs) activated by MIF pretreatment were explored using genomics approaches. Exosome MIF protected cardiomyocytes from H 2 O 2-induced apoptosis. Mechanistically, we identified lncRNA-NEAT1 as a mediator of exosome MIF by regulating the expression of miR-142-3p and activating Forkhead class O1 (FOXO1). The cardioprotective effects of exosome MIF were consistently abrogated by depletion of lncRNA-NEAT1, by overexpression of miR-142-3p, or by FOXO1 silencing. Furthermore, exosome MIF inhibited H 2 O 2-induced apoptosis through modulating oxidative stress. Conclusions: Exosomes obtained from MIF-pretreated MSCs have a protective effect on cardiomyocytes. The lncRNA-NEAT1 functions as an anti-apoptotic molecule via competitive endogenous RNA activity towards miR-142-3p. LncRNA-NEAT1/miR-142-3p/FOXO1 at least partially mediates the cardioprotective roles of exosome MIF in protecting cardiomyocytes from apoptosis.

Long non-coding RNA NEAT1 aggravates epilepsy and seizure-induced neuronal damage by regulating microRNA-139/ROCK1 axis

“…Prior researches have recommended that lncRNA NEAT1 is a critical regulator in malignancy progression, and higher NEAT1 expression is connected with cell metastasis and invasion [19][20][21]. LncRNA NEAT1 has also been validated to be connected with sepsis-induced myocardial cell injury and the cardiomyocyte apoptosis induced by H 2 O 2 [22,23]. Interestingly, a study also found that NEAT1 affected cell viability and inflammatory reaction in epilepsy cell model induced by IL-1β [24].…”

Exosomal LncRNA–NEAT1 derived from MIF-treated mesenchymal stem cells protected against doxorubicin-induced cardiac senescence through sponging miR-221-3p

“…The exosome quick extraction solution was added to the filtered solution at a 1:5 ratio and stored at 4 °C for at least 12 h. The precipitation (exosomes) was dissolved in PBS and stored at − 70 °C. The characterization of exosomes was carried out as previously reported [ 19 ].…”

“…A previous study showed that regaining MIF function attenuated cardiac injury [ 18 ]. Beneficial cardioprotective effects of exosomes derived from MSCs have also been reported in the pretreatment with MIF [ 19 ]. Given the potential therapeutic benefits of exosomes derived from MSCs pretreated with MIF (exosome MIF ), whether MIF pretreatment could affect the functions of exosomes in treating Dox-related cardiac senescence process needs to be determined.…”

“…Intriguingly, the existence of long noncoding RNAs (lncRNAs) in exosomes has been reported, suggesting that lncRNAs may also be loaded with exosomes to regulate gene expression in host cells via cell-to-cell communication [ 20 ]. LncRNA–NEAT1 is located on chromosome 11 and has been indicated to play a significant role in the cardioprotective process through MSC-derived exosome transfer [ 19 ]. Besides, the participation of lncRNA–NEAT1 has been elucidated to be beneficial in the inhibition of Dox-induced cardiotoxicity and apoptosis [ 21 ].…”

“…A target ceRNA of lncRNA–NEAT1, miR-221-3p, impaired tissue regeneration through inhibiting the sirtuin (Sirt) family of proteins [ 23 ]. A previous study reported that exosome-transferred LncRNA–NEAT1 activated the Sirt protein family to exert a cardioprotective effect [ 19 ].…”