Novel Long Non-coding RNA Expression Profile of Peripheral Blood Mononuclear Cells Reveals Potential Biomarkers and Regulatory Mechanisms in Systemic Lupus Erythematosus

Abstract

ObjectiveThe multisystem involvement and high heterogeneity of systemic lupus erythematosus (SLE) lead to great challenges in its diagnosis and treatment. The purpose of this study was to find new lncRNAs in peripheral blood mononuclear cells of SLE patients by transcriptome sequencing and explore their potential as biomarkers and their correlation with clinical features.Materials and MethodsTranscriptome sequencing was used to screen differentially expressed lncRNAs (DELs) and mRNAs (DEMs). The expression of these selected lncRNAs and mRNAs in SLE patients and healthy controls was verified by qPCR. DAVID and WebGestalt were used to perform enrichment analysis. Cytoscape was used to construct a protein–protein network, a coexpression network, and a competitive endogenous RNA network to reveal the regulatory mechanisms of lncRNAs at the transcriptome level.ResultsA total of 1737 DELs and 4078 DEMs were identified between SLE patients and healthy controls. Ten lncRNAs and eight genes were verified by qPCR in a larger sample set. The lncRNA NONHSAT101022.2 was significantly downregulated in SLE patients and was also significantly related to the activity and severity of disease. The upregulated genes were enriched in defense and the immune response, while the downregulated genes were mainly enriched in SLE-related pathways. Topology network analysis revealed that the lncRNAs were involved in regulation at the transcriptome level, including acting directly on mRNA or indirectly affecting gene expression by acting on miRNA.ConclusionIn this work, we identified many mRNAs and novel lncRNAs by transcriptome sequencing. The functions and regulatory mechanisms of these lncRNAs were analyzed by bioinformatic methods. The novel lncRNA NONHSAT101022.2 is significantly downregulated in SLE patients and is significantly related to the activity and severity of disease. Additionally, we propose that NONHSAT101022.2 may enhance the signal transduction of β2-AR by cis regulating LMBRD2, inducing NK cells to produce high levels of IFN-γ and thereby exacerbating SLE.

Integrative Analysis for Elucidating Transcriptomics Landscapes of Systemic Lupus Erythematosus

“…The results indicated that these common DEGs may lead to the occurrence and development of SLE. Previous studies had shown that lncRNA and circRNA are important factors leading to the occurrence of SLE ( Cheng et al, 2021 ; Jiang et al, 2021 ). We found that the differential expression of these common DEGs might play an important role in this process.…”

“…GSE162828 included 10 samples of peripheral blood mononuclear cells and was divided into the SLE group (5 samples) and healthy controls group (5 samples). GSE169080 included seven samples of peripheral blood mononuclear cells and was divided into SLE group (4 samples) and healthy controls group (3 samples) ( Clough and Barrett, 2016 ; Cheng et al, 2021 ; Jiang et al, 2021 ).…”

“…Cheng. et al based on the genome-wide expression data of peripheral blood mononuclear cells (PBMC) of SLE patients found a novel marker of SLE ( Cheng et al, 2021 ). Jiang.…”

Long non‐coding RNAs in systemic lupus erythematosus: New insights into disease pathogenesis and diagnosis

“…We proposed that NONHSAT101022.2 may exacerbate SLE by promoting NK cells to secrete IFN‐γ by cis‐regulating LMBRD2 (LMBR1 Domain Containing 2) to amplify the β2‐AR signal transduction. Further functional experiments need to be performed 82 …”

Progress in the application of body fluid and tissue level mRNAs-non-coding RNAs for the early diagnosis and prognostic evaluation of systemic lupus erythematosus

“…The expression of lncRNAs directly affects in the occurrence and development of SLE and may be related to organ damage, clinical symptoms, and changes in biomarkers of disease activity and progression. The downregulation of the lncRNA NONHSAT101022.2 in the peripheral blood of SLE patients may increase β2-AR signal transduction via cis-regulation of LMBRD2, thereby inducing natural killer cells to produce high levels of IFN-γ and worsening the progression of SLE ( 84 ). The expression of AC007278.2 continues to increase in the peripheral blood of SLE patients, which regulates autoimmunity and follicular T helper cell differentiation by affecting the expression of CCR7, AZU1, and TNIP3 ( 85 ).…”