LncRNA HOTAIR inhibits the progression of fibroblast-like synoviocytes by sponging miRNA-106b-5p in rheumatoid arthritis

Qiu, Hai-Rong; Liu, Meixia; Shi, Xuefei; Ma, Miao; Zhang, Jing; Liu, Hua

doi:10.1080/08916934.2022.2126460

Cited by 11 publications

(10 citation statements)

References 50 publications

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“…Co-culture of differentiated monocytes with HOTAIR-silenced SF, but not the addition of HOTAIR-silenced SF supernatants, decreased osteoclast formation, suggesting that cell-cell contact was necessary to inhibit osteoclastogenesis. Thus, the decrease in osteoclastogenesis after HOTAIR silencing could be related to the reduced migratory function of SF silenced for HOTAIR, which was also observed in another study (44). Another explanation is that the decrease in osteoclastogenesis is mediated by the decreased CXCL12 secretion following HOTAIR silencing(52), as osteoclasts co-cultured with HOTAIR silenced SF but also incubated with supernatants showed decreased osteoclast activity (41).…”

Section: Discussionsupporting

confidence: 57%

“…Here, we showed that HOTAIR expression in SF is decreased after stimulation by local inflammatory factors, which could explain this decreased expression in RA SF. Other recent studies have shown that HOTAIR expression could be regulated by various factors in the local microenvironment, such as hypoxia (43), hormons (24) or inflammatory factors (44).…”

Section: Discussionmentioning

confidence: 99%

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The long-non coding RNA HOTAIR as site specific regulator of inflammation in chronic arthritis

Elhaï¹,

Micheroli

Houtman

et al. 2023

Preprint

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Most forms of arthritis, have a distinctive topographical pattern of joint involvement. Beyond these differences among diseases, there are also differences in phenotype and response to treatment between joints of the same type of arthritis, suggesting that molecular mechanisms may differ depending on joint location. Here we show that there are joint-specific molecular and tissue changes in the synovium and in local stromal cells (synovial fibroblasts;SF). The long non-coding RNA HOTAIR, expressed only in lower extremities SF, regulates much of this site-specific gene expression in SF. Downregulation of HOTAIR after TNF stimulation regulated relevant inflammatory pathways by epigenetic and transcriptional mechanisms and modified the migratory function of SF, decreased SF-mediated osteoclastogenesis, and increased the attraction of B cells by SF. Since site-specific expression of HOTAIR was also measured in the skin, spine and gastrointestinal tract, we propose HOTAIR as important epigenetic factor that modulates site-specific phenotypes of chronic inflammation.

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Section: Discussionsupporting

confidence: 57%

Section: Discussionmentioning

confidence: 99%

The long-non coding RNA HOTAIR as site specific regulator of inflammation in chronic arthritis

Elhaï¹,

Micheroli

Houtman

et al. 2023

Preprint

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“…As our knowledge of the transcriptome space expands, it is becoming increasingly clear that LncRNAs have multiple microRNA recognition binding sites as competing endogenous RNAs (ceRNAs) or natural microRNA sponges that can eliminate the endogenous repression of their target transcripts by miRNAs. For example, LncRNA‐EWSAT1 can induce apoptosis and inhibit proliferation by affecting RA‐FLS through downregulation of miR‐326 levels, 12 LncRNA XIST binding to GATA1 leads to upregulation of CCN6, which causes RA to enter the inflammatory response phase by altering synovial fibroblast proliferation and angiogenic activity, 13 and LncRNA HOTAIR affects FLSsl growth and apoptosis by regulating miR‐106b‐5p/Smad signaling and thus 14 . These reports suggest that these aberrantly expressed LncRNAs regulate the inflammatory and oxidative stress effects of RA.…”

Section: Discussionmentioning

confidence: 99%

Exploring the effect of LncRNA DANCR to regulate the Keap1‐Nrf2/ARE pathway on oxidative stress in rheumatoid arthritis

Cai,

Sun,

Wang

et al. 2024

Immunity Inflam & Disease

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IntroductionAberrant expression of long noncoding RNAs (LncRNAs) can regulate oxidative stress in rheumatoid arthritis (RA). This study focused on investigating the effects of LncRNA differentiation antagonizing nonprotein coding RNA (DANCR) regulation of Keap1‐Nrf2/ARE pathway on inflammation and oxidative stress in RA.MethodsThe levels of LncRNA DANCR/miR‐486‐3p/Keap1 in peripheral blood of 30 RA groups and 30 normal subjects were examined, and the association of LncRNA DANCR with inflammatory indicators of RA was investigated. We stimulated fibroblast‐like synoviocytes (FLS) from RA patients with tumor necrosis factor α and subsequently performed in vitro cellular assays to construct overexpression plasmids and small interfering RNAs of LncRNA DANCR to investigate the relationship between LncRNA DANCR and FLSs viability and migration in RA, as well as the effects on cellular oxidative stress factors and Keap1‐Nrf2/ARE pathway; molecular biology analysis was used to predict microRNAs that can bind LncRNA DANCR, and luciferase verified the binding sites of LncRNA DANCR with Keap1 and miR‐486‐3p; to further refine the gene and protein expression results, we used reverse transcription‐quantitative polymerase chain reaction and immunoblotting assays.ResultsIn both groups of peripheral blood mononuclear cells, the expression levels of LncRNA DANCR and Keap1 messenger RNA were higher in the RA group than in the normal control group, and the opposite was true for miR‐486‐3p; LncRNA DANCR was positively correlated with total antioxidant capacity (TAOC), IL6, IL17, malondialdehyde (MDA), but not with IL11, rheumatoid factor, cyclic citrullinated peptide, superoxide dismutase (SOD), with 28‐joint disease activity score, reactive oxygen species, C‐reactive protein, and erythrocyte sedimentation rate were negatively correlated; overexpression of LncRNA DANCR stimulated the Keap1‐Nrf2/ARE pathway, decreased the expression of IL10, SOD, TAOC, and increased the expression levels of MDA, IL11, IL‐17, PD‐L1, and silencing of LncRNA DANCR was the opposite, but knockdown of miR‐486‐3p or overexpression of keap1 reversed the expression of the above‐mentioned inflammatory and oxidative factors. In addition, pcDNA‐DANCR clearly showed stronger cell invasion and migration ability and exacerbated its inflammatory response, which may be related to the regulatory role of miR‐486‐3p and Keap1‐Nrf2/ARE signaling pathway, and we verified their targeting relationship using dual luciferase, showing that DANCR could regulate Keap1‐Nrf2/ARE through miR‐486‐3p modulates the Keap1‐Nrf2/ARE pathway and affects inflammatory and oxidative responses in RA patients.ConclusionThe low‐expressed LncRNA DANCR may regulate the Keap1‐Nrf2/ARE pathway and suppress the inflammatory and oxidative responses in RA patients.

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“…Previous research has shown that the expression of the LncRNA HOTAIR is noticeably increased in individuals with RA incontrast to healthy controls 15 . In addition, studies have shown that transfecting RA‐FLS with small interfering RNA (siRNA) targeting lncRNA HOTAIR leads to decreased proliferation, invasion, and migration abilities compared to overexpressed groups 16 . The activation of the phosphoinositide 3‐kinase/protein kinase B (PI3K/AKT) signaling pathway can significantly enhance the proliferation, migration, and tubule formation of human umbilical vein endothelial cells (HUVECs).…”

Section: Introductionmentioning

confidence: 99%

“…15 In addition, studies have shown that transfecting RA-FLS with small interfering RNA (siRNA) targeting lncRNA HOTAIR leads to decreased proliferation, invasion, and migration abilities compared to overexpressed groups. 16 The activation of the phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) signaling pathway can significantly enhance the proliferation, migration, and tubule formation of human umbilical vein endothelial cells (HU-VECs). Moreover, this pathway exhibits potent antiangiogenic effects both in vivo and in vitro.…”

Section: Introductionmentioning

confidence: 99%

LncRNA HOTAIR regulates the PI3K/AKT pathway via the miR‐126‐3p/PIK3R2 axis to participate in synovial angiogenesis in rheumatoid arthritis

Liu,

Wang,

Huang

et al. 2023

Immunity Inflam & Disease

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BackgroundThe abnormal expression of long noncoding RNA (LncRNA) HOTAIR has been associated with synovial angiogenesis in rheumatoid arthritis (RA). The aim of this study is to investigate whether LncRNA HOTAIR plays a role in synovial angiogenesis in RA by regulating the phosphoinositide 3‐kinase/protein kinase B (PI3K/AKT) pathway through the miR‐126‐3p/PIK3R2 axis.MethodsIn this study, we conducted in vitro experiments by designing overexpression plasmids and small interfering RNAs targeting LncRNA HOTAIR and then transfected them into rheumatoid arthritis fibroblast‐like synoviocytes (RA‐FLS). We then co‐cultured the RA‐FLS with human umbilical vein endothelial cells (HUVEC) to establish a RA‐FLS‐induced HUVEC model. We investigated the effects of LncRNA HOTAIR on the proliferation, migration, lumen forming ability of HUVEC, as well as the expression of synovial endothelial cell markers, angiogenic factors, and the PI3K/AKT pathway. To validate the interactions between LncRNA HOTAIR, miR‐126‐3p, and PIK3R2, we used bioinformatics and luciferase reporter experiments. We also employed real‐time fluorescence quantitative, Western blotanalysis, and immunofluorescence techniques to analyze the target genes and proteins.ResultsThe expression of LncRNA HOTAIR was upregulated in HUVEC induced by RA‐FLS. The overexpression of LncRNA HOTAIR significantly increased the expression of vascular endothelial growth factor, basic fibroblast growth factor, CD34, and CD105 in HUVEC, promoting their proliferation, migration, and lumen formation. At the same time, the overexpression of LncRNA HOTAIR inhibited the expression of miR‐126‐3p, promoted the expression of PIK3R2, activated the PI3K/AKT pathway, and promoted the expression of PI3K, AKT and phosphorylated‐AKT, while the silence of LncRNA HOTAIR reversed these expressions. Bioinformatics and double luciferase reporter gene experiments confirmed the targeting relationship among LncRNA HOTAIR, miR‐126‐3p, and PIK3R2. Finally, the rescue experiments showed that PI3K agonists could reverse the inhibitory effect of silent LncRNA HOTAIR on HUVEC.ConclusionLncRNA HOTAIR has the potential to activate the PI3K/AKT pathway, likely through the regulatory axis involving miR‐126‐3p/PIK3R2, consequently contributing to synovial angiogenesis in RA.

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LncRNA HOTAIR inhibits the progression of fibroblast-like synoviocytes by sponging miRNA-106b-5p in rheumatoid arthritis

Cited by 11 publications

References 50 publications

The long-non coding RNA HOTAIR as site specific regulator of inflammation in chronic arthritis

The long-non coding RNA HOTAIR as site specific regulator of inflammation in chronic arthritis

Exploring the effect of LncRNA DANCR to regulate the Keap1‐Nrf2/ARE pathway on oxidative stress in rheumatoid arthritis

LncRNA HOTAIR regulates the PI3K/AKT pathway via the miR‐126‐3p/PIK3R2 axis to participate in synovial angiogenesis in rheumatoid arthritis

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