Basic Information
Regular Relationship :
Phenotype/DiseaseSpecieLupus Nephritis
CeRNA1NEAT1[LncRNA]
miRNAmiR-146b[miRNA]
CeRNA2TRAF6[mRNA]
Tissue/Cell lineHuman Renal Mesangial Cells
SpecieHomo sapiens (human)
CitationCell Tissue Res. 2020 Dec;382(3):627-638. doi: 10.1007/s00441-020-03248-z. Epub 2020 Jul 24.
Reference title
LncRNA NEAT1 accelerates renal mesangial cell injury via modulating the miR-146b/TRAF6/NF-kB axis in lupus nephritis.
Experimental verification
Dual-luciferase reporter assay;ELISA;qRT-PCR;Western blot;Flow Cytometry assay;Luciferase reporter assay;
Functional description
Although growing advances have been made in the regulation of lupus nephritis recently, lupus nephritis is still one of the major causes of death in SLE patients and the pathogenesis remains largely unknown. Therefore, exploring the pathological mechanisms is urgently needed for designing and developing novel therapeutic strategies for lupus nephritis. Human renal mesangial cells (HRMCs) were transfected with sh-NEAT1, miR-146b mimic, pcDNA-NEAT1, miR-146b inhibitor, or sh-TRAF6 to modify their expression. Lipopolysaccharide (LPS) was used to induce inflammatory injury. Cell viability was examined with CCK8. Apoptosis was determined by flow cytometry and Hoechst staining. qRT-PCR and western blot were used to analyze gene expression. The secretion of inflammatory cytokines was examined with ELISA. The bindings of NEAT1 with miR-146b and miR-146b with TRAF6 were tested by dual-luciferase reporter assay. NEAT1 was upregulated in LPS-treated HRMCs. Both the knockdown of NEAT1 and TRAF6 suppressed the LPS-induced inflammatory injury in HRMCs. NEAT1 directly targeted miR-146b to control miR-146b-mediated regulation of TRAF6 expression in HRMCs. NEAT1 promoted the expression of TRAF6 via targeting miR-146b to accelerate the LPS-mediated renal mesangial cell injury in HRMCs. Moreover, TRAF6 activated the NF-kB signaling in HRMCs. NEAT1 accelerated renal mesangial cell injury via directly targeting miR-146b, promoting the expression of TRAF6, and activating the NF-kB signaling in lupus nephritis. Our investigation elucidated novel pathological mechanisms and provided potential therapeutic targets for lupus nephritis.
Annotations
External Annotation for NEAT1 |
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LncRNA-associated competing triplets and functions. |
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Comprehensive experimentally supported associations between lncRNA and human cancer. |
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Infer genomic variations that disturb lncRNA-associated ceRNA regulation.. |
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Provide and annotate disease or phenotype-associated variants in human long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) or their regulatory elements. |
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Providing cellular-specific lncRNA-associated ceRNA networks predicted via high-throughput analysis of single-cell genomic data. |
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Information on all annotated and predicted human genes. |
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Gene nomenclature, gene families and associated resources (genomic, proteomic, phenotypic information). |
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Genome browser for vertebrate genomes. |
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An annotated collection of all publicly available DNA sequences. |
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A wiki-based platform for community curation of human long non-coding RNAs. |
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An integrated knowledge database dedicated to non-coding RNAs. |
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An integrated database of human annotated lncRNA transcripts. |
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Comprehensive annotations of eukaryotic long non-coding RNAs. |
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Comprehensive experimentally supported associations between lncRNA and human cancer. |
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A comprehensive, authoritative compendium of human genes and genetic phenotypes. |
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The catalogue of somatic mutations in cancer. |
