MiR-1224 downregulation inhibits OGD/R-induced hippocampal neuron apoptosis through targeting Ku protein

Abstract

Ischemic cerebrovascular disease is the main cause of disability due to stroke. This study aimed to investigate the function of miR-1224 in OGD/R-induced hippocampal neuron apoptosis, as well as the regulatory mechanism of miR-1224 in ischemic cerebrovascular disease. The oxygen-glucose deprivation/reperfusion (OGD/R) model of primary mouse hippocampal neurons was established. RT-qPCR detected miR-1224, Ku70 and Ku86 levels. Western blotting was applied to measure the expression of Ku70/86 and apoptosis related proteins. Flow cytometry was used to assess apoptosis. JC-1 fluorescence was performed to test the mitochondrial membrane potential (MMP) in neurons. The double luciferase reporter assay was performed to investigate the relationship between miR-1224 and Ku70/86. OGD/R induced the apoptosis and mitochondrial injury in neuronal cells, while miR-1224 downregulation or Ku70/86 upregulation reversed this phenomenon. Meanwhile, miR-1224 negatively regulated the expression of Ku70/86 in neuronal cells through directly targeting Ku70/86. Furthermore, knockdown of Ku70/86 significantly reversed the inhibitory effect of miR-1224 silencing on apoptosis and mitochondrial injury in OGD/R-treated neuronal cells. Our findings indicated that miR-1224 downregulation suppressed OGD/R-induced hippocampal neuron apoptosis by targeting Ku protein, suggesting that miR-1224 could serve as a new target for ischemic cerebrovascular disease treatment.

Bioinformatic analysis of circular RNA expression profiles in a rat lumbosacral spinal root avulsion model

“…Previous studies showed that apoptosis was implicated in the pathophysiology of both central and peripheral nerve injury (Eldadah and Faden, 2000;Jia et al, 2020), and our previous work demonstrated that neuronal apoptosis was also induced in LSRA and might be a key factor restricting the surgical repair effects (Jiang et al, 2014;Zhou et al, 2019c). Specifically, among the predicted miRNAs, rno-miR-1224 and rno-miR-326-5p have been reported to be involved in neuronal apoptosis (Huang et al, 2021;Wan and Xiao, 2022), suggesting that they are likely to be involved in LSRA by regulating neuronal apoptosis. Moreover, we also identified differentially expressed mRNAs targeted by rno-miR-1224 and rno-miR-326-5p, and KEGG pathway analysis revealed that these mRNAs were also significantly enriched apoptosis-associated signaling pathway.…”

“…Of the five miRNAs, rno-miR-1224 and rno-miR-326-5p were previously reported to be involved in neuronal apoptosis (Huang et al, 2021;Wan and Xiao, 2022), and our previous studies demonstrated that neuronal apoptosis might be a key physiological process in LSRA (Jiang et al, 2014;, Frontiers in Genetics frontiersin.org 2019c). To construct a circRNA/miRNA/mRNA network related to neuronal apoptosis, we further predicted targeted mRNAs of rno-miR-1224 and rno-miR-326-5p, and intersected them with differentially expressed mRNAs identified by RNA-seq.…”

Expression Profiles of Long Noncoding RNAs and Messenger RNAs in a Rat Model of Spinal Cord Injury

“…Overexpression of miR-1224 inhibits hepatocyte proliferation and promotes apoptosis, according to Roy et al [ 58 ]. A study by Wan and Xiao found that downregulating miR-1224 prevented neuronal apoptosis and mitochondrial damage caused by OGD/R [ 59 ]. We speculate that lncRNA NONRATT019701.2 and lncRNA XR_001838273.1 may have the potential to regulate the proliferation of microglia and glial cells.…”