Long noncoding RNA NEAT1 sponges miR‐495‐3p to enhance myocardial ischemia‐reperfusion injury via MAPK6 activation

Abstract

The biological function of long noncoding RNA NEAT1 has been revealed in a lot of diseases. Nevertheless, it is still not yet clear whether NEAT1 can modulate the process of myocardial ischemia-reperfusion injury (M-I/R). Here, we reported that NEAT1 was able to sponge miR-495-3p to contribute to M-I/R injury through activating mitogen-activated protein kinase 6 (MAPK6). First, elevated expression of NEAT1 was revealed in M-I/R injury mice, meanwhile, lactate dehydrogenase (LDH) and creatine kinase-muscle/brain (CK-MB) were also upregulated in the serum.Meanwhile, as previously reported, miR-495 serves as a tumor suppressor or an oncogenic miRNA in different types of cancer. Currently, we found miR-495-3p was remarkably reduced in M-I/R mice. Additionally, NEAT1 was significantly induced whereas miR-495-3p was greatly reduced by H 2 O 2 treatment in H9C2 cells.Moreover, loss of NEAT1 in H9C2 cells could repress the viability and proliferation of cells. For another, overexpression of NEAT1 exhibited an opposite phenomenon. Furthermore, LDH release and caspase-3 activity were obviously triggered by upregulation of NEAT1 while suppressed by NEAT1 knockdown. miR-495-3p was indicated and validated as a target of NEAT1 using the analysis of bioinformatics.Interestingly, we observed that miR-495-3p mimics repressed tumor necrosis factorα (TNF-α), interleukin-1β (IL-1β), and IL-18 protein expression while their levels were enhanced by the inhibition of miR-495-3p in H9c2 cells. Subsequently, it was manifested that MAPK6 was a target of miR-495-3p, which could exert a lot in the NEAT1/miR-495-3p-mediated M-I/R injury. Overall, our results implied that NEAT1 contributed to M-I/R injury via the modulation of miR-495-3p and MAPK6. K E Y W O R D SIR injury, MAPK6, miR-495-3p, NEAT1

[Retracted] CircANXA2 Promotes Myocardial Apoptosis in Myocardial Ischemia‐Reperfusion Injury via Inhibiting miRNA‐133 Expression

“…Myocardial ischemia-reperfusion injury (MIRI) refers to the myocardial blood supply interruption within a short period of time; after the recovery of blood supply within a certain period of time, the primary ischemic myocardial injury is more serious than that during ischemia. MIRI mechanism has not been fully elucidated; it is generally believed that the reperfusion outbreak of free radicals, calcium overload, mitochondrial damage, adenosine triphosphate (ATP) energy metabolic disorders, cell autophagy, apoptosis and necrosis, and inflammation is ischemia-reperfusion injury (IRI) pathological process; the main reasons for the occurrence and development connect with each other between the injury mechanisms, often triggering or indirectly causing damage to another [ 5 – 7 ].…”

Knockdown of lncRNA TTTY15 alleviates myocardial ischemia–reperfusion injury through the miR‐374a‐5p/FOXO1 axis

“…To further explore the lncRNA and related miRNA interaction mechanism regulatory network, bioinformatics analysis was conducted to predict the potential lncRNA target of miR-374a-5p ( Figure 1a). Consistent with previous reports, 21,22 the expression of FOXD3-AS1 and NEAT1 was upregulated in H9c2 cardiomyocytes under H/R. Our results showed that TTTY15, a Y-chromosomal lncRNA, was also upregulated.…”

Retracted Article: Long non-coding RNA NEAT1 accelerates cell progression in cervical cancer by regulating the miR-889-3p/E2F7 axis through the activation of the PI3K/AKT pathway

“…22,23 For example, NEAT1 positively contributes to myocardial ischemia-reperfusion injury by interacting with miR-495-3p and activating MAPK6. 24 In addition, when NEAT1 is present in high levels, it promotes cell proliferation and migration by absorbing miR-302a-3p to regulate RELA in pancreatic ductal adenocarcinoma. Consistently, the up-regulation of NEAT1 accelerates cell progression in melanoma by improving E2F3 via miR-495-3p sponging.…”