LncRNA Expression Profiles in Systemic Lupus Erythematosus and Rheumatoid Arthritis: Emerging Biomarkers and Therapeutic Targets

Abstract

Systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) are two common multisystem autoimmune diseases that share, among others, many clinical manifestations and serological features. The role of long non-coding RNAs (lncRNAs) has been of particular interest in the pathogenesis of autoimmune diseases. Here, we aimed to summarize the roles of lncRNAs as emerging novel biomarkers and therapeutic targets in SLE and RA. We conducted a narrative review summarizing original articles on lncRNAs associated with SLE and RA, published until November 1, 2021. Based on the studies on lncRNA expression profiles in samples (including PBMCs, serum, and exosomes), it was noted that most of the current research is focused on investigating the regulatory mechanisms of these lncRNAs in SLE and/or RA. Several lncRNAs have been hypothesized to play key roles in these diseases. In SLE, lncRNAs such as GAS5, NEAT1, TUG1, linc0949, and linc0597 are dysregulated and may serve as emerging novel biomarkers and therapeutic targets. In RA, many validated lncRNAs, such as HOTAIR, GAS5, and HIX003209, have been identified as promising novel biomarkers for both diagnosis and treatment. The shared lncRNAs, for example, GAS5, may participate in SLE pathogenesis through the mitogen-activated protein kinase pathway and trigger the AMP-activated protein kinase pathway in RA. Here, we summarize the data on key lncRNAs that may drive the pathogenesis of SLE and RA and could potentially serve as emerging novel biomarkers and therapeutic targets in the coming future.

Interaction between Long Noncoding RNAs and Syncytin-1/Syncytin-2 Genes and Transcripts: How Noncoding RNAs May Affect Pregnancy in Patients with Systemic Lupus Erythematosus

“…SLE patients exhibit a dysregulated ncRNA signature that results in the increased expression of transcripts and antigenic proteins derived from HERV members or lncRNAs [14,15,[21][22][23][24][25][26]. This event may depend on the SLE cytokine milieu, hormones, chemicals or microbial stimuli [27,28].…”

Epigenetic regulation and T-cell responses in endometriosis – something other than autoimmunity

“…In addition to miRNAs, long noncoding RNAs (lncRNAs), defined as ≥200 base pairs in length with little or no translation potential, play a key role in imprinting control, immune cell differentiation, apoptosis, and immune responses. Many potential lncRNAs have been revealed to contribute to a new layer of molecular regulation of systemic lupus erythematosus (SLE) (166). LncRNAs play an indispensable role in SLE by interacting with proteins, DNA, and even RNA.…”

LncRNA H19 facilitates polarization of M1 phenotype macrophages via miR-145-5p/PAI-1 axis in mediating systemic lupus erythematosus

“…Several studies have validated that lncRNAs are of significance in regulating M1 or M2 macrophage-type polarization, especially in cancers [12]. However, there exists limited knowledge of specific lncRNAs in different macrophages within SLE patients [13]. Although high-throughput methods have been utilized to explore lncRNAs expression profiles in SLE by detecting blood samples, further studies are still needed to investigate their functional mechanisms in mediating SLE in details.…”