Altered long noncoding RNA profile after intracerebral hemorrhage

Abstract

ObjectiveWe investigated the expression pattern of long noncoding RNAs (lncRNA) and messenger RNAs (mRNA) from two different intracerebral hemorrhage (ICH) rat models, and performed gene ontology and gene/protein interaction analyses.MethodsWe harvested hemorrhagic brain 1, 3, and 7 days after ICH induction by stereotactic collagenase injection. We performed microarray analyses with Agilent array platform to compare the expression of lncRNA and mRNAs from hemorrhagic and normal brains. The RNA expression patterns were also examined from the autologous blood injection ICH model at days 1 and 3, and significantly altered lncRNAs from two ICH models were validated by quantitative reverse transcriptase‐polymerase chain reaction. Gene ontology analysis and pathway analysis were performed with differentially expressed mRNAs after ICH. Gene and protein interaction analysis was performed to elucidate the functional role of upregulated lncRNA in neuronal damage.ResultsAmong the 13,661 lncRNAs studied, 83, 289, and 401 lncRNAs were significantly elevated after 1, 3, and 7 days after collagenase‐induced ICH, respectively. NR_027324, or H19, was the most upregulated lncRNA after 1 day from the two ICH models and its elevation persisted until the 7th day. Gene ontology analysis revealed that immune‐related biological processes such as immune response, immune system process, and defense response were upregulated from both ICH models. Gene and protein interaction study demonstrated that NR_027324 was closely related to the type I interferon signaling pathway.InterpretationThis study illustrates the dynamic expression pattern of the lncRNA profile following ICH, and that H19 is the most consistently upregulated lncRNA after ICH.

LncRNAs Stand as Potent Biomarkers and Therapeutic Targets for Stroke

“…This study first revealed the temporal expression pattern of lncRNAs with an acute hemorrhagic stroke model induced by stereotactic collagenase injection. Gene ontology/pathway analysis revealed that inflammation is a key biological process after a hemorrhagic stroke and functional study disclosed that lncRNA H19 was the most upregulated lncRNA after intracerebral hemorrhage and closely related to the type I interferon signaling pathway (Kim et al, 2019). Therefore, lncRNA H19 plays an important role both in ischemic stroke and intracerebral hemorrhage.…”

“…The role of lncRNAs in intracerebral hemorrhage is an attractive field that scientists have tried to elucidate with limited success. Kim et al (2019) performed microarray analyses and found that 83, 289, and 401 lncRNAs were significantly upregulated, whereas 52, 489, and 786 lncRNAs were significantly decreased of 1, 3, and 7 days after intracerebral hemorrhage, respectively. This study first revealed the temporal expression pattern of lncRNAs with an acute hemorrhagic stroke model induced by stereotactic collagenase injection.…”

“…Thereafter, altered lncRNA expression profiles have been investigated in rodent focal cerebral ischemia models, ischemic stroke patients as well as in vitro cultured cells following oxygen and glucose deprivation/reoxygenation (OGD/R; Zhao et al, 2015;Zhang et al, 2016;Guo et al, 2018). Kim et al (2019) investigated the expression pattern of lncRNA from two different intracerebral hemorrhage rat models. The aberrant expression of lncRNAs uncovered in stroke has led researchers to explore the potential roles and mechanisms of specific lncRNA in brain physiology and pathology.…”

Genetic Aspects of Inflammation and Immune Response in Stroke

“…LncRNAs are consisted of more than 200 nucleotides, although, less abundant compared to miRs they show more microenvironment-dependent function [ 70 ] and have regulatory roles in a variety of metabolic processes in the nucleus and cytoplasm [ 71 ]. In recent years, the function of different lncRNAs in expression regulation after stroke is studied more extensively, especially in inflammation [ 72 , 73 , 74 ]. Interestingly, lncRNA may regulate the expression of genes coding for miRs.…”

RNA-seq Identifies circRNAs Expression Profiles and Potential Biomarkers for Intracerebral Hemorrhage

“…Peripheral blood cells play vital roles in the brain injury caused by ICH, and previous studies have reported that noncoding RNA (ncRNA) expression pro les are altered rapidly in the blood [9][10][11]. CircRNAs are a large class of ncRNAs produced by back-splicing [12].…”