LncRNA THRIL aggravates sepsis-induced acute lung injury by regulating miR-424/ROCK2 axis

Chen, Huibin; Hu, Xuemei; Li, Ruiting; Liu, Boyi; Zheng, Xiang; Fang, Zhicheng; Chen, Li; Chen, Wei; Li, Min; Hu, S. Jack

doi:10.1016/j.molimm.2020.07.021

Cited by 43 publications

(29 citation statements)

References 44 publications

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“…The administration of microRNA can selectively regulate the expression of diverse mRNA, modulating cell responses. In this way, the use of microRNA in sepsis and endotoxemia can reduce pulmonary inflammation by inhibiting RhoA/ROCK activation [151,152].…”

Section: Rho Proteins and Their Impact On Sepsis Outside The Cardiovascular Systemmentioning

confidence: 99%

Rho-Proteins and Downstream Pathways as Potential Targets in Sepsis and Septic Shock: What Have We Learned from Basic Research

Hahmeyer

Silva-Santos

2021

Cells

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Sepsis and septic shock are associated with acute and sustained impairment in the function of the cardiovascular system, kidneys, lungs, liver, and brain, among others. Despite the significant advances in prevention and treatment, sepsis and septic shock sepsis remain global health problems with elevated mortality rates. Rho proteins can interact with a considerable number of targets, directly affecting cellular contractility, actin filament assembly and growing, cell motility and migration, cytoskeleton rearrangement, and actin polymerization, physiological functions that are intensively impaired during inflammatory conditions, such as the one that occurs in sepsis. In the last few decades, Rho proteins and their downstream pathways have been investigated in sepsis-associated experimental models. The most frequently used experimental design included the exposure to bacterial lipopolysaccharide (LPS), in both in vitro and in vivo approaches, but experiments using the cecal ligation and puncture (CLP) model of sepsis have also been performed. The findings described in this review indicate that Rho proteins, mainly RhoA and Rac1, are associated with the development of crucial sepsis-associated dysfunction in different systems and cells, including the endothelium, vessels, and heart. Notably, the data found in the literature suggest that either the inhibition or activation of Rho proteins and associated pathways might be desirable in sepsis and septic shock, accordingly with the cellular system evaluated. This review included the main findings, relevance, and limitations of the current knowledge connecting Rho proteins and sepsis-associated experimental models.

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Section: Rho Proteins and Their Impact On Sepsis Outside The Cardiovascular Systemmentioning

confidence: 99%

Rho-Proteins and Downstream Pathways as Potential Targets in Sepsis and Septic Shock: What Have We Learned from Basic Research

Hahmeyer

Silva-Santos

2021

Cells

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“…As previously reported, THRIL is a multifunctional lncRNA that has important roles in various cellular p r o c e s s e s b y t r a n s c r i p t i o n a l r e g u l a t i o n o f g e n e expression (17) and post-transcriptional regulation, such as targeting microRNAs (25,38). Our data indicate that the modulation of THRIL in the invasion and proliferation of RA FLSs might be associated with its role in regulating the gene expression of CDK1 and GTSE1.…”

Section: Discussionmentioning

confidence: 93%

LncRNA THRIL is involved in the proliferation, migration, and invasion of rheumatoid fibroblast-like synoviocytes

Zou¹,

Shen²,

Shen³

et al. 2021

Ann Transl Med

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Background: Fibroblast-like synoviocytes (FLSs), which can migrate and directly invade the cartilage and the bone, are crucial players in joint damage in rheumatoid arthritis (RA). Nevertheless, the detailed mechanisms underlying the aberrant activation of RA FLSs remain unclear. Several studies have attempted to explore the relationship between long non-coding RNAs (lncRNAs) and RA pathology; however, the role of lncRNAs in RA is unknown. The present study aimed to determine the functions of tumor necrosis factor-α and heterogeneous nuclear ribonucleoprotein L-related immunoregulatory lincRNA (THRIL) in RA FLSs migration and invasion.Methods: Small interfering RNA targeting THRIL or lentivirus overexpressing THRIL was used to knockdown or overexpress THRIL. Quantitative reverse transcription polymerase chain reaction (PCR) was employed for the detection of RNA expression. The proliferation rate of RA FLSs was measured using a 5-ethynyl-2'-deoxyuridine (EdU) incorporation assay. Migration and invasion were detected using a transwell chamber. Downstream targets were identified using a human cell cycle real-time PCR array and a human cell motility real-time PCR array.Results: A significant decrease in THRIL expression was found in RA FLSs compared with cells from healthy control (HC)patients. THRIL is mainly localized in the nucleus. Knockdown of THRIL increased the proliferation, migration, and invasion of RA FLSs. In contrast, THRIL overexpression had the opposite effect. THRIL knockdown increased interleukin-1β (IL-1β)-triggered expression of matrix metalloproteinase (MMP)-1, MMP-3, and MMP-13. THRIL overexpression led to a significant decrease in MMP-13 expression in response to stimulation with IL-1β. Furthermore, we observed that the expression levels of cyclindependent kinase 1 (CDK1) and G2 and S phase-expressed-1 (GTSE1), both of which are associated with cellular mobility and proliferation, were downregulated with THRIL overexpression.Conclusions: Reduced expression of lncRNA THRIL represses the proliferation, migration, and invasion of RA FLSs, suggesting that lncRNA THRIL might be a potential target for RA therapy.

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“…Knockdown of lncRNA-THRIL effectively reduced the lung injury in mice and inhibited the release of factor- α , IL-1 β , IL-6, and other cytokines. In their in vitro experiments, lncRNA-THRIL upregulated ROCK2 levels through sponging miR-424 to promote the apoptosis of vascular endothelial cells and the release of inflammatory cytokines [ 21 ]. Wang et al reported that downregulation of lncRNA CASC9 inhibited LPS-induced injury in human small airway epithelial cells by regulating the miR-195-5p/PDK4 axis [ 22 ].…”

Section: Discussionmentioning

confidence: 99%

lncRNA-SNHG14 Plays a Role in Acute Lung Injury Induced by Lipopolysaccharide through Regulating Autophagy via miR-223-3p/Foxo3a

Hong

Gong

et al. 2021

Mediators of Inflammation

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lncRNAs play important roles in lipopolysaccharide- (LPS-) induced acute lung injury. But the mechanism still needs further research. In the present study, we investigate the functional role of the lncRNA-SNHG14/miR-223-3p/Foxo3a pathway in LPS-induced ALI and tried to confirm its regulatory effect on autophagy. Transcriptomic profile changes were identified by RNA-seq in LPS-treated alveolar type II epithelial cells. The expression changes of lncRNA-SNHG14/miR-223-3p/Foxo3a were confirmed using qRT-PCR and west blot. The binding relationship of lncRNA-SNHG14/miR-223-3p/and miR-223-3p/Foxo3a was verified using dual-luciferase reporter, RNA immunoprecipitation, and RNA pull-down assays. Using gain-of-function or loss-of-function approaches, the effect of lncRNA-SNHG14/miR-223-3p/Foxo3a was investigated in LPS-induced acute lung injury mice model and in vitro. Increasing of lncRNA-SNHG14 and Foxo3a with reducing miR-223-3p was found in LPS-treated A549 cells and lung tissue collected from the LPS-induced ALI model. lncRNA-SNHG14 inhibited miR-223-3p but promoted Foxo3a expression as a ceRNA. Artificially changes of lncRNA-SNHG14/miR-223-3p/Foxo3a pathway promoted or protected cell injury from LPS in vivo and in vitro. Autophagy activity could be influenced by lncRNA-SNHG14/miR-223-3p/Foxo3a pathway in cells with or without LPS treatment. In conclusion, aberrant expression changes of lncRNA-SNHG14 participated alveolar type II epithelial cell injury and acute lung injury induced by LPS through regulating autophagy. One underlying mechanism is that lncRNA-SNHG14 regulated autophagy by controlling miR-223-3p/Foxo3a as a ceRNA. It suggested that lncRNA-SNHG14 may serve as a potential therapeutic target for patients with sepsis-induced ALI.

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LncRNA THRIL aggravates sepsis-induced acute lung injury by regulating miR-424/ROCK2 axis

Cited by 43 publications

References 44 publications

Rho-Proteins and Downstream Pathways as Potential Targets in Sepsis and Septic Shock: What Have We Learned from Basic Research

Rho-Proteins and Downstream Pathways as Potential Targets in Sepsis and Septic Shock: What Have We Learned from Basic Research

LncRNA THRIL is involved in the proliferation, migration, and invasion of rheumatoid fibroblast-like synoviocytes

lncRNA-SNHG14 Plays a Role in Acute Lung Injury Induced by Lipopolysaccharide through Regulating Autophagy via miR-223-3p/Foxo3a

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