Expression and functional analysis of lncRNAs in the hippocampus of immature rats with status epilepticus

Abstract

Long non‐coding RNAs (lncRNAs) have been implicated in the regulation of gene expression at various levels. However, to date, the expression profile of lncRNAs in status epilepticus (SE) was unclear. In our study, the expression profile of lncRNAs was investigated by high‐throughput sequencing based on a lithium/pilocarpine‐induced SE model in immature rats. Furthermore, weighted correlation network analysis (WGCNA), gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed to construct co‐expression networks and establish functions of the identified hub lncRNAs in SE. The functional role of a hub lncRNA (NONRATT010788.2) in SE was investigated in an in vitro model. Our results indicated that 7082 lncRNAs (3522 up‐regulated and 3560 down‐regulated), which are involved in cell proliferation, inflammatory responses, angiogenesis and autophagy, were dysregulated in the hippocampus of immature rats with SE. Additionally, WGCNA identified 667 up‐regulated hub lncRNAs in turquoise module that were involved in apoptosis, inflammatory responses and angiogenesis via regulation of HIF‐1, p53 and chemokine signalling pathways and via inflammatory mediator regulation of TRP channels. Knockdown of an identified hub lncRNA (NONRATT010788.2) inhibited neuronal apoptosis in vitro. Taken together, our study is the first to demonstrate the expression profile and potential function of lncRNAs in the hippocampus of immature rats with SE. The defined hub lncRNAs may participate in the pathogenesis of SE via lncRNA‐miRNA‐mRNA network.

Excitotoxic stimulation activates distinct pathogenic and protective expression signatures in the hippocampus

“…As compared to the early changes in biological function nodes, delayed changes exhibited the inclusion of nodes for ion transport, cytoskeleton organization and neurotransmitter transport, thus suggesting repair/compensatory responses and energy‐dependent processes were activated. Interestingly, in addition to the wide range of functional categories among NMDA‐induced up‐ and down‐regulated genes, long non‐coding RNAs (lncRNAs) assessed in a young rat model of lithium/pilocarpine‐induced status epilepticus were found to exhibit up‐ and down‐regulation for wide functional influence 55 …”

“…Interestingly, in addition to the wide range of functional categories among NMDA-induced up-and down-regulated genes, long non-coding RNAs (lncRNAs) assessed in a young rat model of lithium/pilocarpine-induced status epilepticus were found to exhibit up-and down-regulation for wide functional influence. 55 The F I G U R E 5 Distinct and biphasic activation of NF-κB in the excitotoxic hippocampus. NMDA was infused into hippocampal explants for 20 min, followed by rapid washout and antagonist quenching for the defined insult to compare to non-treated control tissue (NT The present study supports the idea that the brain is not a passive recipient of pathogenic insults and the induction of degenerative processes, but rather, the brain can trigger pathways of cellular repair that counter pathological responses to injury.…”

“…Interestingly, in addition to the wide range of functional categories among NMDA‐induced up‐ and down‐regulated genes, long non‐coding RNAs (lncRNAs) assessed in a young rat model of lithium/pilocarpine‐induced status epilepticus were found to exhibit up‐ and down‐regulation for wide functional influence. 55 The modified lncRNAs identified were found to influence the regulation of genes involved in cell proliferation, inflammation, angiogenesis and autophagy.…”

Integrative analysis provides multi‐omics evidence for the pathogenesis of placenta percreta

“…LncRNAs exert diverse roles in cellular and biological processes via the regulation of gene expression and chromatin dynamics 21 . Recently, lncRNAs have been shown to contribute to the pathogenesis of various diseases, including cancer, 22‐24 cardiovascular disease 25 and nervous system diseases 26 . The deregulation of lncRNAs IGF2/H19, MEG3, SPRY4‐IT1, HOTAIR, MALAT1, FLT1P1 and CEACAMP8 in placental trophoblasts is involved in the pathogenesis of preeclampsia 27 .…”

“…21 Recently, lncRNAs have been shown to contribute to the pathogenesis of various diseases, including cancer, [22][23][24] cardiovascular disease 25 and nervous system diseases. 26 The deregulation of lncRNAs IGF2/H19, MEG3, SPRY4-IT1, HOTAIR, MALAT1, FLT1P1 and CEACAMP8 in placental trophoblasts is involved in the pathogenesis of preeclampsia. 27 Among them, lncRNA MALAT1 may be involved in the pathogenesis of preeclampsia via the regulation of the proliferation, cell cycle, apoptosis, migration and invasion of trophoblast cells.…”