Long Non-coding RNA N1LR Protects Against Myocardial Ischemic/Reperfusion Injury Through Regulating the TGF-β Signaling Pathway

Abstract

Long non-coding RNAs (lncRNAs) have been shown to play critical roles in various cell biological processes. However, the mechanism of lncRNAs in acute myocardial infarction (AMI) is not fully understood. Previous studies showed that lncRNA N1LR was down-regulated in ischemic cerebral stroke and its up-regulation was protective. The current study was designed to assess the protective effect of N1LR and further to explore potential mechanisms of N1LR in ischemic/reperfusion (I/R) injury after AMI. Male C57BL/6J mice and H9c2 cardiomyocytes were selected to construct in vivo and in vitro pathological models. In H9c2 cell line, N1LR expression was markedly decreased after H2O2 and CoCl2 treatments and N1LR overexpression alleviated apoptosis, inflammation reaction, and LDH release in cardiomyocytes treated with H2O2 and CoCl2. Mouse in vivo study showed that overexpression of N1LR enhanced cardiac function and suppressed inflammatory response and fibrosis. Mechanistically, we found that the expression of transforming growth factor (TGF)-β1 and smads were significantly decreased in the N1LR overexpression group exposed to H2O2. In a summary, our study indicated that N1LR can act as a protective factor against cardiac ischemic-reperfusion injury through regulating the TGF-β/Smads signaling pathway.

Potential diagnostic value of N1LR and SNHG1 in acute myocardial infarction

“…Compared with control group, the expression level of N1LR in AMI group was significantly lower (Fig. 1 A, P < 0.001), which was consistent with the previous animal model [ 10 ]. To evaluate the predictive power of N1LR in AMI diagnosis, an ROC curve was drawn.…”

“…N1LR has been firstly reported as a novel I/R-induced lncRNA and possesses the ability to be neuroprotective in ischemic mice model that overexpression of N1LR could ameliorate the H2O2-induced cell apoptosis, inflammation response, death, and LDH release by prevention of p53 in vitro [ 8 , 10 ]. Taken together, these results may indicate that N1LR could be a potential factor to protect neurons to ischemic injury.…”

“…Thus, exploring lncRNA in clinical practice may assist in disease diagnosis and finding the potential therapeutic target. N1LR was initially found to be involved in ischemic stroke via p53 inhibition [ 9 ] and upregulation of N1LR was proved to be protective after I/R induced injury via repressing TGF-β1 pathway to inhibit H 2 O 2 -induced apoptosis, inflammatory response and LDH release in cardiomyocyte [ 10 ]. SNHG1, another lncRNA, was first identified by its oncogenic promotion in cancer cell proliferation, and an increased level of SNHG1 was associated with decreased survival rate [ 11 ].…”

The Role of ncRNAs in Cardiac Infarction and Regeneration

“…Several other lncRNAs modulate the expression of distinct miRNAs that influence signaling pathways leading to fibrosis, such as Mhrt/miR-3185, n379519/miR-30, and Xist/miR-155, although the precise affected signaling pathways remain unclear [ 121 , 147 , 210 ]. Finally, a series of lncRNAs are reported to modulate TGF-β1/Smad signaling, such as lncRNA554, Lnc-Ang362, LncR-30245, and NILR, yet the molecular mechanisms remain to be elucidated [ 211 , 212 , 213 , 214 ]. Importantly, FGD5-AS1 lncRNA can modulate both processes, i.e., inflammation and fibrosis, through miR-223 sponging and thus the modulation of Akt signaling [ 91 ].…”

Dioscin Alleviates Cardiac Dysfunction in Acute Myocardial Infarction via Rescuing Mitochondrial Malfunction

“…Transthoracic echocardiographic analysis was performed 2 weeks after the sham or MI surgery as previously described (13). Echocardiography on unconscious mice was used with a Vevo 2100 system (VisualSonics).…”