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Catalogue of differentially expressed long non-coding RNAs following activation of human and mouse innate immunity

ABSTRACT: Despite increasing evidence to indicate that long non-coding RNAs (lncRNAs) are novel regulators of immunity, there has been no systematic attempt to identify and characterise the lncRNAs whose expression are changed following the induction of the innate immune response. To address this issue, we have employed next generation sequencing data to determine the changes in the lncRNA profile in LPS-stimulated human macrophages, IL1beta-stimulated human airway A549 epithelial cells and and LPS-stimulated mouse RAW 264.7 macrophages

OTHER RELATED OMICS DATASETS IN: PRJNA395745

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE101868 | GEO | 2017/10/01

SECONDARY ACCESSION(S): PRJNA395745

REPOSITORIES: GEO

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Project description:Long noncoding RNAs (lncRNAs) have emerged as novel regulators of macrophage biology and related inflammatory cardiovascular diseases. However, studies focused on lncRNAs in human macrophage subtypes, particularly human lncRNAs that are not conserved in rodents, are limited. Through RNA-seq of human monocyte-derived macrophages, we identified Suppressor of Inflammatory Macrophage Apoptosis lncRNA (SIMALR), a human macrophage-specific long intergenic noncoding RNA, to be highly induced in LPS/IFNγ-stimulated macrophages. Treatment of LPS/IFNγ stimulated THP1 human macrophages with SIMALR antisense oligonucleotides induced apoptosis of inflammatory macrophages, as shown by increased protein expression of cleaved PARP, caspase 9, caspase 3, and Annexin V+. RNA-seq of control versus SIMALR knockdown in LPS/IFNγ-stimulated human monocyte derived macrophages showed NTN1 to be significantly decreased upon SIMALR knockdown. As expected, NTN1 knockdown in LPS/IFNγ-stimulated macrophages induced apoptosis. This apoptotic phenotype was attenuated by adding recombinant NTN1 after SIMALR knockdown. Furthermore, NTN1 promoter-luciferase reporter activity was increased in HEK293T cells treated with lentiviral overexpression of SIMALR. NTN1 promoter activity is known to require HIF1α. RNA immunoprecipitation and microscopy studies suggest that SIMALR may interact with HIF1α to regulate NTN1 transcription, thereby regulating apoptosis of macrophages. In translational studies, SIMALR was found to be expressed in macrophages in human carotid atherosclerotic plaques of symptomatic patients. SIMALR is a non-conserved, human macrophage lincRNA expressed in human atherosclerosis that regulates macrophage apoptosis. SIMALR partners with HIF1α to regulate NTN1, which is a known macrophage survival factor. This work illustrates the importance of interrogating the functions of non-conserved human lincRNAs and exploring their translational and therapeutic potential in human atherosclerosis.

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Catalogue of differentially expressed long non-coding RNAs following activation of human and mouse innate immunity

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