Long Non-coding RNA HIX003209 Promotes Inflammation by Sponging miR-6089 via TLR4/NF-κB Signaling Pathway in Rheumatoid Arthritis

Yan, Shushan; Wang, Pingping; Wang, Jinghua; Yang, Jinghan; Lu, Hongying; Jin, Chengwen; Cheng, Min; Xu, Dongmei

doi:10.3389/fimmu.2019.02218

Cited by 94 publications

(73 citation statements)

References 44 publications

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“…Furthermore, PVT1 was explored to significantly decrease miR-365 expression in Huh7 and HepG2 cells through sponging effect through the luciferase reporter assay [21]. During the past decade, the ceRNA theory involving lncRNA-miRNA-mRNA network has been established in the progression of various kinds of disorders, including autoimmune diseases [22]. For instance, a novel lncRNA GAPLINC has been monitored to encourage tumor-like behaviors of RA-FLS through binding with miR-382-5p and miR-575 [23].…”

Section: Discussionmentioning

confidence: 99%

Knockdown of long non-coding RNA PVT1 induces apoptosis of fibroblast-like synoviocytes through modulating miR-543-dependent SCUBE2 in rheumatoid arthritis

Wang

Kong

et al. 2020

J Orthop Surg Res

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Background: Rheumatoid arthritis (RA), a kind of autoimmune disorder, is featured by many physical symptoms and proliferation of fibroblast-like synoviocytes (FLSs). The relevance of long non-coding RNAs (lncRNAs) in the progression of RA has been probed. Hence, the goal of this report was to investigate the action of plasmacytoma variant translocation 1 (PVT1), a lncRNA, in FLSs and the basic mechanism. Methods: Initially, RA rats were developed to evaluate the expression of PVT1, microRNA-543 (miR-543), and signal peptide-CUB-EGF-like containing protein 2 (SCUBE2) in synovial tissues. Enhancement or loss of PVT1 or miR-543 was achieved to explore their effects on proliferation, cell cycle, and apoptosis of FLSs. The interaction between PVT1 and miR-543 and between miR-543 and its putative target SCUBE2 was examined to elucidate the correlations. Finally, the protein expression of proliferation-and apoptosis-associated genes were assessed by western blot assays. Results: PVT1 was overexpressed in synovial tissues from RA patients through microarray expression profiles. The PVT1 and SCUBE2 expression was boosted, and miR-543 was reduced in synovial tissues of rats with RA. PVT1 specifically bound to miR-543, and miR-543 negatively regulated SCUBE2 expression. Overexpression of PVT1 or silencing of miR-543 enhanced SCUBE2 expression, thereby promoting proliferation and interleukin-1β (IL-1β) secretion, while inhibiting apoptosis rate of FLSs. Conversely, si-SCUBE2 reversed the role of miR-543 inhibitor. Conclusion:The key findings support that PVT1 knockdown has the potency to hinder RA progression by inhibiting SCUBE2 expression to sponge miR-543.

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Section: Discussionmentioning

confidence: 99%

Knockdown of long non-coding RNA PVT1 induces apoptosis of fibroblast-like synoviocytes through modulating miR-543-dependent SCUBE2 in rheumatoid arthritis

Wang

Kong

et al. 2020

J Orthop Surg Res

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“…miR-126 inhibited the methylation of promoter region in CD70 and CD11a to promote the expression of CD11a and CD70 (50). The binding of miR-6089 and lncRNA-HIX003209 promoted the expression of TLR4 and exacerbates inflammation through the TLR4/NF-κB pathway in macrophages (51). miR-30a could increase inflammation by aggravating autophagy and reducing apoptosis (52).…”

Section: Mirnas Mediated Innate and Adaptive Immune Cell Differentiatmentioning

confidence: 99%

Epigenetic Regulation Mediated by miRNA in the Susceptibility and Pathogenesis of Rheumatoid Arthritis

Guo¹,

Chang²,

Xu³

et al. 2020

Preprint

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Contribution:micro-RNA (miRNA) has been demonstrated to play important roles in the transcriptome regulation and disease development including cancer and autoimmune disease such as rheumatoid arthritis. However, a comprehensive role of miRNAs in rheumatoid arthritis (RA) including immune system differentiation and interaction with terminal cells like T cells, fibroblast-like synoviocytes (FLS), osteoblast and osteoclast still unclear. In this review, we have provided a thorough summary on the roles of miRNAs in the susceptibility, pathogenesis, diagnosis, therapeutic intervention and prognosis. We summarized the blood and cell-free miRNA biomarkers which provided novel opportunity to work together with rheumatoid factors (RF), anti-CCP to provide accurate diagnosis and prognosis especially for seronegative patients. Finally, miRNAs were showed as promising biomarker to indicate the DMRDS and immunotherapy efficiency, drug response and resistance. What's more, autotherapeutic effect of miRNA intervention provided promising to develop miRNA based rheumatoid arthritis drugs. Overall, current evidence supports miRNAs as the interesting targets to better understand the pathogenetic mechanism and therapeutic intervention of rheumatoid arthritis.Preprints (www.preprints.org) | NOT PEER-REVIEWED | Posted: 15 April 2020 Abstract micro-RNA (miRNA) has been demonstrated to play important roles in the transcriptome regulation and disease development including cancer and autoimmune disease such as rheumatoid arthritis. However, a comprehensive map on how the mRNAs regulate transcripts, pathways, immune system differentiation and interaction with terminal cells like T cells, fibroblast-like synoviocytes (FLS), osteoblast and osteoclast still unknown. In this review, we have provided a thorough summary on the roles of miRNAs in the susceptibility, pathogenesis, diagnosis, therapeutic intervention and prognosis. Numerous miRNAs were found abnormally expressed in rheumatoid arthritis relevant cells and regulated the target genes and pathways like NF-κB, Fas-FasL, JAK-STAT, IRE1-RIDD, mTOR pathway. In addition, miRNA act as gene expression regulators affect the T cell differentiate to different cell types including Th17 and T-reg cells which provide promising gene therapy target to regulate immune systems in rheumatoid arthritis. We also summarized interesting diagnosis and prognosis roles of blood and cell-free based miRNAs which provided novel opportunity to work together with rheumatoid factors (RF), anti-CCP to provide accurate diagnosis and prognosis especially for seronegative patients. Furthermore, functional genetic variants in miR-499 and miR-146a explained part of missing susceptibility of rheumatoid arthritis. Finally, miRNAs were showed as promising biomarker to indicate the DMRDS and immunotherapy efficiency, drug response and resistance. What's more, autotherapeutic effect of miRNA intervention provided promising to develop miRNA based rheumatoid arthritis drugs. Overall, current evidence supports miRNAs as the inter...

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“…For example, miR-126 inhibits methylation of the promoter region in CD70 and CD11a, thereby promoting their expression (Yang et al, 2015). In macrophages, binding of miR-6089 and lncRNA-HIX003209 enhances the expression of TLR4 and exacerbates inflammation through the TLR4/NF-κB pathway (Yan et al, 2019). In addition, miR-30a can increases inflammation, by aggravating autophagy and reducing apoptosis (Xu et al, 2013).…”

Section: Mirna-mediated Innate and Adaptive Immune Cell Differentiatimentioning

confidence: 99%

Epigenetic Regulation Mediated by microRNAs in the Susceptibility and Pathogenesis of Rheumatoid Arthritis

Guo¹,

Chang²,

Xu³

et al. 2020

Preprint

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MicroRNAs (miRNAs) play crucial roles in the regulation of the transcriptome and development of diseases including cancer and autoimmune diseases, such as rheumatoid arthritis (RA). Currently, a comprehensive map, illustrating how miRNAs regulate transcripts, pathways, immune system differentiation, and their interaction with terminal cells, such as T cells, fibroblast-like synoviocytes (FLS), osteoblasts, and osteoclasts, is still missing. In this review, we provide a thorough summary of the roles of miRNAs in the susceptibility to pathogenesis, diagnosis, therapeutic intervention, and prognosis of RA. Numerous miRNAs are abnormally expressed in cells involved in RA, and regulate target genes and pathways including the NF-κB, Fas-FasL, JAK-STAT, IRE1-RIDD, and mTOR pathways. By regulating gene expression, miRNAs affect T cell differentiation to diverse cell types, including Th17 and T-reg cells, and thus constitute promising gene therapy targets to modulate the immune system in RA. We summarize the diagnostic and prognostic potential of blood-circulating and cell-free miRNAs, highlighting the novel opportunities to combine these with rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) to provide accurate diagnosis and prognosis, especially for seronegative patients. Furthermore, we outline how functional genetic variants of miR-499 and miR-146a partly explain the unmet susceptibility to RA. Additionally, we review the evidence implicating miRNAs as promising biomarkers of efficiency, response, and resistance to disease-modifying anti-rheumatic drugs (DMRDs) and immunotherapy. Finally, we discuss the autotherapeutic effect of miRNA intervention as a step toward the development of miRNA-based anti-RA drugs. Collectively, the current evidence supports miRNAs as interesting targets to better understand the pathogenetic mechanisms of RA and design more efficient therapeutic interventions.

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Long Non-coding RNA HIX003209 Promotes Inflammation by Sponging miR-6089 via TLR4/NF-κB Signaling Pathway in Rheumatoid Arthritis

Cited by 94 publications

References 44 publications

Knockdown of long non-coding RNA PVT1 induces apoptosis of fibroblast-like synoviocytes through modulating miR-543-dependent SCUBE2 in rheumatoid arthritis

Knockdown of long non-coding RNA PVT1 induces apoptosis of fibroblast-like synoviocytes through modulating miR-543-dependent SCUBE2 in rheumatoid arthritis

Epigenetic Regulation Mediated by miRNA in the Susceptibility and Pathogenesis of Rheumatoid Arthritis

Epigenetic Regulation Mediated by microRNAs in the Susceptibility and Pathogenesis of Rheumatoid Arthritis

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