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. 2023 Mar;21(1):e2.
doi: 10.5808/gi.22061. Epub 2023 Mar 31.

Comprehensive investigation of the expression profiles of common long noncoding RNAs during microglial activation

Janghyun Kim  1 , Bora Lee  2 , Young Kim  3 , Byeong C Kim  1   4 , Joon-Tae Kim  1   4 , Hyong-Ho Cho  5
Affiliations

Comprehensive investigation of the expression profiles of common long noncoding RNAs during microglial activation

Janghyun Kim et al. Genomics Inform. 2023 Mar.

Abstract

Microglia, similar to peripheral macrophages, are the primary immune cells of the central nervous system (CNS). Microglia exist in the resting state in the healthy CNS, but can be activated and polarized into either M1 or M2 subtypes for immune defense and the maintenance of CNS homeostasis by multiple stimuli. Several long noncoding RNAs (lncRNAs) mediate human inflammatory diseases and neuropathologies by regulating their target genes. However, the function of common lncRNAs that contribute to microglial activation remains unclear. Thus, we used bioinformatic approaches to identify common lncRNAs involved in microglial activation in vitro. Our study identified several lncRNAs as common regulators of microglial activation. We identified 283 common mRNAs and 53 common lncRNAs during mouse M1 microglial activation processes, whereas 26 common mRNAs and five common lncRNAs were identified during mouse M2 microglial activation processes. A total of 648 common mRNAs and 274 common lncRNAs were identified during the activation of human M1 microglia. In addition, we identified 1,920 common co-expressed pairs in mouse M1 activation processes and 25 common co-expressed pairs in mouse M2 activation processes. Our study provides a comprehensive understanding of common lncRNA expression profiles in microglial activation processes in vitro. The list of common lncRNAs identified in this study provides novel evidence and clues regarding the molecular mechanisms underlying microglial activation.

Keywords: M1 microglia activation; M2 microglia activation; lnc-miRHGs; long noncoding RNA; microglia.

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Conflict of interest statement

Conflicts of Interest

No potential conflict of interest relevant to this article was reported.

Figures

Fig. 1.
Fig. 1.
Expression of interleukin 6 (IL-6) and arginase-1 (Arg1) in lipopolysaccharide (LPS)-stimulated (A, C) and IL-4–stimulated microglia (B). Transcripts per million (TPM) were used to measure gene expression levels. Error bars represent standard deviation. The p-value was calculated using the Subread-DESeq2 pipeline. Statistical significance is indicated by asterisks (***p < 0.001; ns, not significant).
Fig. 2.
Fig. 2.
Identification of common long noncoding RNAs (lncRNAs) in the lipopolysaccharide (LPS)-induced mouse M1 polarization state. (A) Venn diagrams displaying the overlapping lncRNAs associated with LPS-stimulated mouse M1 microglia from analyses of the GSE75706, GSE79898, GSE80304, GSE90046, and GSE105155 datasets. (B) Bar graphs showing significant differences in the expression levels of lncRNAs, expressed as log2-fold change values, across five different datasets. (C) The identified lncRNAs in their genomic context. Genomic information was visualized with the Gviz package. Mir155hg contains the Mir155 sequence, and Mir22hg contains the Mir22 sequence. F630028O10Rik contains the Mir223 sequence. The p-values were calculated using the Subread-DESeq2 pipeline. Statistical significance is indicated by asterisks (*p < 0.05, **p < 0.01, ***p < 0.001).
Fig. 3.
Fig. 3.
Identification of common long noncoding RNAs (lncRNAs) in the lipopolysaccharide (LPS)-induced human M1 polarization state. (A) Venn diagrams displaying the overlapping lncRNAs associated with LPS-stimulated human M1 microglia from the GSE133432 #1 and GSE133432 #2 analyses. (B) Bar graphs showing significant differences in the expression levels of lncRNAs, expressed as log2-fold change values, across 2 different datasets. (C) The genomic context of the identified lncRNAs. Genomic information was visualized with the Gviz package. MIR155HG contains the MIR155 sequence, and MIR3142HG contains the MIR3142 and MIR146a sequences. MIR201HG contains the MIR210 sequence. The p-values were calculated using the Subread-DESeq2 pipeline. Statistical significance is indicated by asterisks (**p < 0.01, ***p < 0.001).
Fig. 4.
Fig. 4.
Identification of common long noncoding RNAs (lncRNAs) in the interleukin 4 (IL-4)–induced mouse M2 polarization state. (A) Venn diagrams displaying the overlapping lncRNAs associated with IL-4–stimulated mouse M2 microglia from the analysis of GSE70383 and GSE157891. (B) Bar graphs showing the significant differences in the expression levels of lncRNAs, expressed as log2-fold change values, across two different datasets. (C) The identified lncRNAs in their genomic context. Genomic information was visualized with the Gviz package. The lncRNA Mir99ahg contains the Mir99a, Mirlet7c, and Mir125b sequences. The lncRNA 1700086P04Rik and lncRNA Gm36172 have overlapping promoters of Rnf19b and Arg1. The p-value was calculated using the Subread-DESeq2 pipeline. Significance is indicated by asterisks (*p < 0.05, **p < 0.01, ***p < 0.001).
Fig. 5.
Fig. 5.
Construction of networks of long noncoding RNA (lncRNAs) and mRNAs in the M1 (A) and M2 (B) microglial activation states. The diamond and circular shapes represent lncRNAs and mRNAs, respectively. Red nodes represent upregulated lncRNAs or mRNAs, and blue nodes represent downregulated lncRNAs or mRNAs.
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