Long noncoding RNA NEAT1 sponges miR-495-3p to enhance myocardial ischemia-reperfusion injury via MAPK6 activation.
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 H2 O2 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 factor-α (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.
['Luo|Man|M|', 'Sun|Qingsong|Q|', 'Zhao|Hongmei|H|', 'Tao|Jiali|J|', 'Yan|Dongsheng|D|0000-0002-8002-3856']
D000818:Animals D002460:Cell Line D049109:Cell Proliferation D005786:Gene Expression Regulation D006801:Humans D006861:Hydrogen Peroxide D051379:Mice D008810:Mice, Inbred C57BL D035683:MicroRNAs D015428:Myocardial Reperfusion Injury D062085:RNA, Long Noncoding
NEAT1 miR-495-3p MAPK6 IR injury