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.
Highlights
Intracerebral hemorrhage (ICH) is a devastating stroke subtype with high mortality and profound neurological deficit for survivors.[1]
This study illustrates the Long noncoding RNA (lncRNA) expression pattern of ICH models and found that intergenic lncRNAs undergo the most vigorous expression alteration during the disease process. By applying both microarray and qRT-PCR from two different ICH models, we found that H19 is the most upregulated lncRNA after ICH, which remained significant up to 7 days following hemorrhage
The number of significantly elevated and decreased lncRNAs increased as time passed following ICH, suggesting the dynamic nature of the lncRNA expression machinery induced by ICH
Summary
Intracerebral hemorrhage (ICH) is a devastating stroke subtype with high mortality and profound neurological deficit for survivors.[1]. The novel treatment strategy based on the mechanism of neuronal damage after ICH is a plausible option which can be successfully translated to clinical practice. Long noncoding RNA (lncRNA) is a noncoding RNA with more than 200 base pairs without translational activity; recent studies have shown that they can control gene expression by modulating transcription and translational processes.[3]. Annals of Clinical and Translational Neurology published by Wiley Periodicals, Inc on behalf of American Neurological Association.
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