Knockdown of lncRNA LUCAT1 attenuates sepsis‑induced myocardial cell injury by sponging miR-642a

Wang, Jing; Xin, Shaobin; Yang, Rui; Jiang, Jian; Qiao, You-jie

doi:10.1007/s00335-021-09890-4

Cited by 11 publications

(6 citation statements)

References 28 publications

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“…Several investigations have demonstrated differential expression of lncRNAs, including XIST, NEAT1, SNHG1, LUCAT1, and MALAT1, in myocardial injury-complicated sepsis models in both animals and cells. [20][21][22] Notably, these lncRNAs predominantly govern inflammatory and immune responses, as well as oxidative stress pathways, [23][24][25] which aligns with our findings. Previous studies on the mechanism of myocardial injury related to sepsis primarily focused on the classical nuclear factor κB signaling pathway and cytokine secretion.…”

Section: Discussionsupporting

confidence: 90%

Identification of a Novel lncRNA in Diagnosis of Sepsis-Induced Cardiomyopathy Using a Comprehensive Analysis of lncRNA-mRNA Network

Li,

Liu,

Tang

et al. 2023

J Pediatr Infect Dis

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Objective Long noncoding RNAs (lncRNAs) have been implicated in various biological processes, particularly in the regulation of inflammatory responses and myocardial injuries. Notably, the role of lncRNAs in sepsis-induced cardiomyopathy (SIC) has been highlighted. However, a comprehensive analysis investigating the specific circulating lncRNAs associated with SIC has yet to be conducted. Therefore, we conducted a study involving samples from healthy controls, sepsis patients without myocardial injuries, individuals with cardiac dysfunction following heart surgery, and those with SIC, aiming to identify the distinct lncRNAs involved in SIC. Methods A total of 12 blood samples were collected, including healthy controls, sepsis patients without myocardial injuries, patients with cardiac surgery-related myocardial injuries, and patients with SIC, who were aged from 10 to 22 months. Transcriptome sequencing was conducted to identify differentially expressed (DE) lncRNAs and mRNAs. Venn plots were employed to identify the DE RNAs specific to SIC. Subsequently, enrichment analyses were performed using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes terms. A coexpression network between lncRNAs and mRNAs was constructed, focusing on protein–protein interaction features. Then, further validation had been done in a consecutive larger cohort. Results We identified independent DE mRNAs and lncRNAs specific to SIC patients. The analysis of DE mRNAs revealed that immune activation, particularly innate immune activity, was the primary distinction between sepsis with or without myocardial injuries. Furthermore, cytokine production, particularly interleukin-1 secretion, played a significant role in inducing SIC. The expression profiles of DE lncRNAs showed considerable enrichment in shared topics with mRNAs. Subsequently, we identified lncRNAs targeting the DE mRNAs, many of which were involved in immune responses and cytokine production. We established a coexpression network between lncRNAs and mRNAs, leading to the discovery of a novel lncRNA (TCONS_00136255). Finally, we successfully validated TCONS_00136255, demonstrating its acceptable diagnostic accuracy and its role in regulating major molecular processes involved in SIC. Conclusion lncRNAs actively participate in the significant biological changes associated with immune responses in sepsis-induced myocardial injuries. These lncRNAs interact with mRNAs to modulate inflammation activity and cytokine production. Notably, the identification of the novel lncRNA (TCONS_00136255) highlights its crucial regulatory role in SIC.

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Section: Discussionsupporting

confidence: 90%

Identification of a Novel lncRNA in Diagnosis of Sepsis-Induced Cardiomyopathy Using a Comprehensive Analysis of lncRNA-mRNA Network

Li,

Liu,

Tang

et al. 2023

J Pediatr Infect Dis

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“… 65 Xiao et al also found knockdown of lncRNA LUCAT1 suppressed the release of IL1β, IL6 and TNF-α to attenuate sepsis‑induced myocardial cell injury. 66 Thus, our theory that LUCAT1 exerted pro-inflammatory roles to mediate MWCNT-induced toxicity for ARPE-19 cells may be believable.…”

Section: Discussionmentioning

confidence: 93%

Inflammatory Genes Associated with Pristine Multi-Walled Carbon Nanotubes-Induced Toxicity in Ocular Cells

Luo¹,

Xie²,

Su³

et al. 2023

IJN

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Background The wide application of multi-walled carbon nanotubes (MWCNTs) in various fields has raised enormous concerns regarding their safety for humans. However, studies on the toxicity of MWCNTs to the eye are rare and potential molecular mechanisms are completely lacking. This study was to evaluate the adverse effects and toxic mechanisms of MWCNTs on human ocular cells. Methods Human retinal pigment epithelial cells (ARPE-19) were treated with pristine MWCNTs (7–11 nm) (0, 25, 50, 100 or 200 μg/mL) for 24 hours. MWCNTs uptake into ARPE-19 cells was examined using transmission electron microscopy (TEM). The cytotoxicity was evaluated by CCK-8 assay. The death cells were detected by Annexin V-FITC/PI assay. RNA profiles in MWCNT-exposed and non-exposed cells (n = 3) were analyzed using RNA-sequencing. The differentially expressed genes (DEGs) were identified through the DESeq2 method and hub of which were filtered by weighted gene co-expression, protein–protein interaction (PPI) and lncRNA-mRNA co-expression network analyses. The mRNA and protein expression levels of crucial genes were verified using quantitative polymerase chain reaction (qPCR), colorimetric analysis, ELISA and Western blotting. The toxicity and mechanisms of MWCNTs were also validated in human corneal epithelial cells (HCE-T). Results TEM analysis indicated the internalization of MWCNTs into ARPE-19 cells to cause cell damage. Compared with untreated ARPE-19 cells, those exposed to MWCNTs exhibited significantly decreased cell viabilities in a dose-dependent manner. The percentages of apoptotic (early, Annexin V positive; late, Annexin V and PI positive) and necrotic (PI positive) cells were significantly increased after exposure to IC50 concentration (100 μg/mL). A total of 703 genes were identified as DEGs; 254 and 56 of them were, respectively, included in darkorange2 and brown1 modules that were significantly associated with MWCNT exposure. Inflammation-related genes (including CXCL8, MMP1, CASP3, FOS, CXCL2 and IL11 ) were screened as hub genes by calculating the topological characteristics of genes in the PPI network. Two dysregulated long non-coding RNAs ( LUCAT1 and SCAT8 ) were shown to regulate these inflammation-related genes in the co-expression network. The mRNA levels of all eight genes were confirmed to be upregulated, while caspase-3 activity and the release of CXCL8, MMP1, CXCL2, IL11 and FOS proteins were demonstrated to be increased in MWCNT-treated ARPE-19 cells. MWCNTs exposure also can induce cytotoxicity and increase the caspase-3 activity and the expression of LUCAT1, MMP1, CXCL2, and IL11 mRNA and protein in HCE-T cells. Conclusion Our study provides promising biomarkers for monitoring MWCNT-induced eye disorders and targets for developing preventive and therapeutic strategies.

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“…At present, more and more researches have been conducted to give evidence to support the ceRNA hypothesis that lncRNAs carrying MREs can competitively combine with some miRNAs, thus, at the post-transcriptional stage, controlling miRNA-mediated downstream target gene silencing ( Khorkova et al, 2015 ). For example, Zhang et al ( Zhang et al, 2020 ) have demonstrated that lncRNA TCONS_00016233 aggravates septic acute renal injury induced by LPS by binding to miR-22-3p and preventing the down-regulation of miR-22-3p-mediated apoptosis inducing factor mitochondria associated 1 (AIFM1); Wang et al ( Wang et al, 2021 ) found that lncRNA-LUCAT1 can regulate the expression of ROCK1 in H9C2 cells induced by LPS by secreting miR-642a. Knockout of lncRNALUCA T1 can inhibit myocardial injury in sepsis induced by LPS; An et al ( An et al, 2021 ) believe that LncRNA ZFAS1, as the ceRNA of miR-138-5p, up-regulates the expression of SESN2, thus improving cardiomyocyte scorch death induced by sepsis.…”

Section: Discussionmentioning

confidence: 99%

Construction of a potentially functional lncRNA-miRNA-mRNA network in sepsis by bioinformatics analysis

Zheng

et al. 2022

Front. Genet.

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Objective: Sepsis is a common disease in internal medicine, with a high incidence and dangerous condition. Due to the limited understanding of its pathogenesis, the prognosis is poor. The goal of this project is to screen potential biomarkers for the diagnosis of sepsis and to identify competitive endogenous RNA (ceRNA) networks associated with sepsis.Methods: The expression profiles of long non-coding RNAs (lncRNAs), microRNAs (miRNAs) and messenger RNAs (mRNAs) were derived from the Gene Expression Omnibus (GEO) dataset. The differentially expressed lncRNAs (DElncRNAs), miRNAs (DEmiRNAs) and mRNAs (DEmRNAs) were screened by bioinformatics analysis. DEmRNAs were analyzed by protein-protein interaction (PPI) network analysis, transcription factor enrichment analysis, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and Gene Set Enrichment Analysis (GSEA). After the prediction of the relevant database, the competitive ceRNA network is built in Cytoscape. The gene-drug interaction was predicted by DGIgb. Finally, quantitative real-time polymerase chain reaction (qRT-PCR) was used to confirm five lncRNAs from the ceRNA network.Results: Through Venn diagram analysis, we found that 57 DElncRNAs, 6 DEmiRNAs and 317 DEmRNAs expressed abnormally in patients with sepsis. GO analysis and KEGG pathway analysis showed that 789 GO terms and 36 KEGG pathways were enriched. Through intersection analysis and data mining, 5 key KEGG pathways and related core genes were revealed by GSEA. The PPI network consists of 247 nodes and 1,163 edges, and 50 hub genes are screened by the MCODE plug-in. In addition, there are 5 DElncRNAs, 6 DEmiRNAs and 28 DEmRNAs in the ceRNA network. Drug action analysis showed that 7 genes were predicted to be molecular targets of drugs. Five lncRNAs in ceRNA network are verified by qRT-PCR, and the results showed that the relative expression of five lncRNAs was significantly different between sepsis patients and healthy control subjects.Conclusion: A sepsis-specific ceRNA network has been effectively created, which is helpful to understand the interaction between lncRNAs, miRNAs and mRNAs. We discovered prospective sepsis peripheral blood indicators and proposed potential treatment medicines, providing new insights into the progression and development of sepsis.

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Knockdown of lncRNA LUCAT1 attenuates sepsis‑induced myocardial cell injury by sponging miR-642a

Cited by 11 publications

References 28 publications

Identification of a Novel lncRNA in Diagnosis of Sepsis-Induced Cardiomyopathy Using a Comprehensive Analysis of lncRNA-mRNA Network

Identification of a Novel lncRNA in Diagnosis of Sepsis-Induced Cardiomyopathy Using a Comprehensive Analysis of lncRNA-mRNA Network

Inflammatory Genes Associated with Pristine Multi-Walled Carbon Nanotubes-Induced Toxicity in Ocular Cells

Construction of a potentially functional lncRNA-miRNA-mRNA network in sepsis by bioinformatics analysis

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