LncRNA, regulates the expression of protein-coding genes via functioning as miRNA sponges. Numerous studies have elucidated that lncRNAs extensively participate in crucial physiological processes such as metabolism and immunity, and are closely linked to the emergence and progression of tumors, cardiovascular diseases, nervous system disorders, nephropathy, and other diseases. However, the mechanism of lncRNA-mediated ceRNA in intestinal I/R injury remains unclear. In this study, the expression datasets of miRNA of intestinal I/R injury samples were collected from the NCBI GEO datasets GSE83701. LncRNA and mRNA were predicted by database through miDEGs, and lncRNA 1700020114Rik/mmu-miR-7a-5p/Klf4 ceRNA network was constructed by Cytoscape. The animal experiments validated that LncRNA 1700020I14Rik, Klf4 were downregulated. Meanwhile, miR-7a-5p was up-regulated in intestinal I/R injury. Besides,there has been no report of the 11700020114Rik/mmu-miR-7a-5p/Klf4 ceRNA network in intestinal I/R injury so far.
LncRNA1700020I14Rik is also known as Oip5os1 and Oip5as1.Studies[11, 12] have elucidated that lncRNAs 1700020I14Rik play a key role in apoptosis, cell proliferation and fibrosis, oxidative stress, and other physiological processes. In addition, other studies[11, 13] revealed that LncRNA 1700020I14Rik was downregulated in the hearts of rats with myocardial I/R injury and hypoxia / reoxygenation( H/R )injury in myocardial cells. Researchers discovered that sponging miR-186-5p with up-regulated lncRNA OIP5-AS1 reduced neuron damage in microglia/macrophages following middle cerebral artery occlusion/reperfusion produced inflammation and oxidative stress.
The mmu-miR-7a-5p sequence in Mus musculus is a product of miR-7 genes. miR-7a-5p has controversial roles in multi-organ injury. Some researches[15, 16] found that miR-7a-5p may play a protective role in intestinal and brain. However, other studies demonstrated that miR-7a-5p was up-regulated during the cerebral I/R injury, acute lung injury, and myocardial injury induced by lipopolysaccharide . The qRT-PCR results showed that miR-7a-5p was up-regulated after intestinal I/R injury.
Klf4 can be regulated by miRNA at both transcriptional and post-transcriptional levels. Klf4 is a multi-functional transcription factor that regulates diverse cellular processes in a context-dependent manner. Thus, the role of Klf4 is determined by different genes interacting with Klf4. Hummitzsch et al. found that the expression level of Klf4 was decreased in Human Regulatory Macrophages after H/R. Meanwhile, Klf4 could alleviate lipopolysaccharide-induced inflammation and cerebral vascular injury after cerebral ischemic stroke [22, 23]. Therefore, Klf4 could help to alleviate I/R injury.
Overall, the lncRNA 1700020I14Rik, Klf4 and miR-7a-5p were associated with ischemia/reperfusion injury or oxygen-glucose deprivation injury.
In addition, lncRNA 1700020I14Rik and Klf4 were downregulated, and miR-7a-5p was up-regulated in ischemia/reperfusion injury in the ceRNA network identified by the bioinformatics analysis. This was in accordance with the experimental validation in intestinal I/R injury. Furthermore, studies have confirmed that miR-7a-5p has interactions with Klf4 in acute lung injury.
Therefore, the 1700020114Rik/mmu-miR-7a-5p/Klf4 axis was postulated to play a potential role in intestinal I/R injury. It was the first time to uncover lncRNA mediated ceRNA networks in intestinal I/R injury. However, the role of 1700020114Rik/mmu-miR-7a-5p/Klf4 ceRNA network in intestinal I/R injury needs to be examined in further studies.