Long non-coding RNAs (lncRNAs) NEAT1 and MALAT1 are differentially expressed in severe COVID-19 patients: An integrated single-cell analysis.
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ABSTRACT:
SUBMITTER: Huang K
PROVIDER: S-EPMC8746747 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Hyperactive and damaging inflammation is a hallmark of severe rather than mild COVID-19 syndrome. To uncover key inflammatory differentiators between severe and mild COVID-19 disease, we applied an unbiased single-cell transcriptomic analysis. We integrated a bronchoalveolar lavage (BAL) dataset with a peripheral blood mononuclear cell dataset (PBMC) and analyzed the combined cell population, focusing on genes associated with disease severity. Distinct cell populations were detected in both BAL and PBMC where the immunomodulatory long non-coding RNAs (lncRNAs) NEAT1 and MALAT1 were highly differentially expressed between mild and severe patients. The detection of other severity associated genes involved in cellular stress response and apoptosis regulation suggests that the pro-inflammatory functions of these lncRNAs may foster cell stress and damage. The lncRNAs NEAT1 and MALAT1 are potential components of immune dysregulation in COVID-19 that may provide targets for severity related diagnostic measures or therapy.
| S-EPMC8020982 | biostudies-literature
Project description:Background and objectiveLong non-coding RNAs (lncRNAs) can act as competing endogenous RNAs (ceRNAs) to compete for micro-RNAs (miRNAs) in regulation of downstream genes, various biological functions and diseases. Yet, the expression and regulation of lncRNAs in periodontitis are not fully understood. The objective of the study was to identify potential genes (lncRNA, messenger RNA [mRNA] and miRNA) involved in periodontitis, construct lncRNA-miRNA-mRNA ceRNA networks, explore gene functions and validate gene expressions.Material and methodsThe data sets for the lncRNA, mRNA and miRNA expression profiles in gingival samples from periodontally healthy subjects and chronic periodontitis patients were obtained from the Gene Expression Omnibus. The differentially expressed lncRNAs (DElncRNAs), mRNAs (DEmRNAs) and miRNAs (DEmiRNAs) were identified, and ceRNA networks were then constructed. The expression of DElncRNAs and DEmRNAs was examined by quantitative real-time polymerase chain reaction (qPCR). Moreover, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed for exploring the potential functions and biological pathways.ResultsThe GSE80715 and GSE54710 data sets were retrieved. Subsequently, 26 DElncRNAs, 436 DEmRNAs and 12 DEmiRNAs were identified (|fold change| ≥2, adjusted p < 0.05). Further bioinformatics analysis contributed to establishment of the ceRNA networks, which consisted of 10 DElncRNAs, 11 DEmiRNAs and 83 DEmRNAs. Notably, the qPCR results showed a marked decrease in the expression of lncRNA H19 and two mRNAs (NOS1 and MAPT) which further supported the identified ceRNA network. The GO results revealed that the up-regulated mRNAs were significantly enriched in inflammatory processes, whilst the down-regulated mRNAs were enriched in cellular potentials.ConclusionNon-coding RNAs are critically involved in the regulatory mechanisms in the pathogenesis of periodontitis. Further study is warranted to investigate the specific underlying genetic traits and networks.
| S-EPMC8359208 | biostudies-literature
Project description:Mechanistic roles for many lncRNAs are poorly understood, in part because their direct interactions with genomic loci and proteins are difficult to assess. Using a method to purify endogenous RNAs and their associated factors, we mapped the genomic binding sites for two highly expressed human lncRNAs, NEAT1 and MALAT1. We show that NEAT1 and MALAT1 localize to hundreds of genomic sites in human cells, primarily over active genes. NEAT1 and MALAT1 exhibit colocalization to many of these loci, but display distinct gene body binding patterns at these sites, suggesting independent but complementary functions for these RNAs. We also identified numerous proteins enriched by both lncRNAs, supporting complementary binding and function, in addition to unique associated proteins. Transcriptional inhibition or stimulation alters localization of NEAT1 on active chromatin sites, implying that underlying DNA sequence does not target NEAT1 to chromatin, and that localization responds to cues involved in the transcription process.
| S-EPMC4428586 | biostudies-literature
Project description:Behçet's disease (BD) is a chronic inflammatory disease. Immunological defects have been shown to play a significant role in the progression of BD. The serum levels of two long non-coding RNAs (lncRNAs), NEAT1 and MALAT1, were examined in patients with BD to identify their role in the disease pathogenesis. Both lncRNAs were mentioned as essential regulators of innate immune responses and have a crucial role in inflammatory diseases. Fifty patients with BD and a similar number of control individuals were involved in our study. At enrollment, data was collected from patients and controls, and the disease severity in active cases was determined using the Behçet's Disease Current Activity Form (BDCAF). Levels of the two studied biomarkers in the serum, NEAT1 and MALAT1, were investigated by quantitative RT-PCR (qRT-PCR). NEAT1 levels were significantly turned down in BD patients (fold changes = 0.77, p = 0.0001) and correlated negatively with the BDCAF (r = -0.41; p = 0.003). On the other hand, the MALAT1 levels were significantly up-regulated in BD patients (fold changes = 2.65, p = 0.003). Serum levels of NEAT1 were significantly decreased in patients with active states than in stationary cases (0.387 versus 1.99, respectively; p = 0.01) and compared with controls (p = 0.001). Also, NEAT1 levels were significantly increased in patients with stationary states compared to controls (p = 0.03). There was a positive association between NEAT1 and MALAT1 levels among BD patients (r = 0.29, p = 0.04). Our findings demonstrate a possible role of NEAT1 and MALAT1 in the pathogenesis of BD.
| S-EPMC9253411 | biostudies-literature
Project description:Macrophages display remarkable plasticity, with the ability to undergo dynamic transition between classically and alternatively activated phenotypes. Long non-coding RNAs (lncRNAs) are more than 200 nucleotides in length and play roles in various biological pathways. However, the role of lncRNAs in regulating macrophage polarization has yet to be explored. In this study, lncRNAs expression profiles were determined in human monocyte-derived macrophages (MDMs) incubated in conditions causing activation toward M(IFN-? + LPS) or M(IL-4) phenotypes. Compared with primary MDMs, 9343 lncRNAs and 5903 mRNAs were deregulated in M(IFN-? + LPS) group (fold change ? 2.0, P < 0.05), 4592 lncRNAs and 3122 mRNAs were deregulated in M(IL-4) group. RT-qPCR results were generally consistent with the microarray data. Furthermore, we found that TCONS_00019715 is expressed at a higher level in M(IFN-? + LPS) macrophages than in M(IL-4) macrophages. TCONS_00019715 expression was decreased when M(IFN-? + LPS) converted to M(IL-4) whereas increased when M(IL-4) converted to M(IFN-? + LPS). Knockdown of TCONS_00019715 following the activation of THP-1 cellls using IFN-? and LPS diminished the expression of M(IFN-? + LPS) markers, and elevated the expression of M(IL-4) markers. These data show a significantly altered lncRNA and mRNA expression profile in macrophages exposure to different activating conditions. Dysregulation of some of these lncRNAs may play important roles in regulating macrophage polarization.
| S-EPMC4726337 | biostudies-other
Project description:Long non-coding RNAs (lncRNAs) are subclass of noncoding RNAs that have been recently shown to play critical roles in cancer biology. However, little is known about their mechanistic role in breast cancer pathogenesis, especially in triple-negative breast carcinomas (TNBC) that have particular poor outcomes. This study was specifically designed to identify the signatures relevant lncRNAs in breast cancer and characterize lncRNAs that modulate the phenotype. Here we provide detailed methods and analysis of microarray data, which is deposited in the Gene Expression Omnibus (GEO) with the accession number GSE64790. The basic analysis as contained in the manuscript published in Oncotarget with the PMID 26078338. These data can be used to further elucidate the mechanisms of breast cancer.
| S-EPMC4664755 | biostudies-literature
Project description:BackgroundMolecular regulation related to the health benefits of different exercise modes remains unclear. Long non-coding RNAs (lncRNAs) have emerged as an RNA class with regulatory functions in health and diseases. Here, we analyzed the expression of lncRNAs after different exercise training programs and their possible modes of action related to physical exercise adaptations.MethodsPublic high-throughput RNA-seq data (skeletal muscle biopsies) were downloaded, and bioinformatics analysis was performed. We primarily analyzed data reports of 12 weeks of resistance training (RT), high-intensity interval training (HIIT), and combined (CT) exercise training. In addition, we analyzed data from 8 weeks of endurance training (ET). Differential expression analysis of lncRNAs was performed, and an adjusted P-value < 0.1 and log2 (fold change) ≥0.5 or ≤-0.5 were set as the cutoff values to identify differentially expressed lncRNAs (DELs).ResultsWe identified 204 DELs after 12 weeks of HIIT, 43 DELs after RT, and 15 DELs after CT. Moreover, 52 lncRNAs were differentially expressed after 8 weeks of ET. The lncRNA expression pattern after physical exercise was very specific, with distinct expression profiles for the different training programs, where few lncRNAs were common among the exercise types. LncRNAs may regulate molecular responses to exercise, such as collagen fibril organization, extracellular matrix organization, myoblast and plasma membrane fusion, skeletal muscle contraction, synaptic transmission, PI3K and TORC regulation, autophagy, and angiogenesis.ConclusionFor the first time, we show that lncRNAs are differentially expressed in skeletal muscle after different physical exercise programs, and these lncRNAs may act in various biological processes related to physical activity adaptations.
| S-EPMC7533564 | biostudies-literature
Project description:BackgroundLong non-coding RNAs (lncRNAs) and their polymorphisms play crucial roles in the development of different cancers.MethodsEight single-nucleotide polymorphisms (SNPs) in ANRIL and MALAT1 (rs1333045, rs4977574, rs1333048, and rs10757278 in ANRIL and rs11227209, rs619586, rs664589, and rs3200401 in MALAT1) were enrolled and genotyped in a total of 1248 samples, including 587 patients with cervical cancer (CC) and 661 healthy individuals using in TaqMan assay. The association of these SNPs with CC was then evaluated.ResultsOur results showed that the allele and genotype frequencies of rs3200401 in MALAT1 were significantly different between the control and CC groups after Bonferroni correction (P = 0.001 and P = 0.004, respectively), indicating that the C allele is a protective factor against CC (OR = 0.70; 95% CI = 0.57-0.87). In addition, the allele and genotype frequencies of rs4977574 in ANRIL were significantly different between the control and CC groups after Bonferroni correction (P = 0.004 and P = 0.014, respectively), and the A allele might be a protective factor for CC (OR = 0.80; 95% CI = 0.68-0.93). For subgroup analysis, the alleles of rs3200401 in MALAT1 showed significant differences between the control and adenocarcinoma (AC) and control and squamous cell carcinoma (SCC) groups (P = 0.005 and P = 0.004, respectively). The rs3200401C allele could be a protective factor for AC and SCC development (OR = 0.57; 95% CI = 0.38-0.85; OR = 0.72; 95% CI = 0.58-0.90). Moreover, the rs3200401C allele could be a protective factor for cervical cancer stage I development (OR = 0.67; 95% CI = 0.53-0.86).ConclusionOur results indicate that rs3200401 in MALAT1 and rs4977574 in ANRIL could play key roles in the CC development.
| S-EPMC9037735 | biostudies-literature
Project description:The etiology and pathogenesis of non-syndromic cleft lip and palate (NSCL/P) are largely unknown. Long non-coding RNAs (lncRNA) are thought to play important roles in NSCL/P, but reports on the underlying processes are currently unavailable. Our study focused on children diagnosed with NSCL/P alone. Based on the morphology, patients were categorized as either cleft lip with or without cleft palate (CL/P) or cleft palate-only (CPO). When patients received surgery for NSCL/P, tissue excised from the trimmed wound edge was reserved to serve as experimental samples; adjacent normal tissue was used as a positive control. Target lncRNAs in the collected tissues were identified using microarray and quantitative reverse transcription PCR (RT-qPCR). Immunohistochemical (IHC) staining and RT-qPCR were used to verify the target mRNAs. Pathway, gene ontology (GO) enrichment, and TargetScan prediction were employed to construct endogenous RNA networks (ceRNA networks) and explore their potential functions. RNA-Seq analysis revealed 24 upregulated and 43 downregulated lncRNAs in the CL/P and CPO groups compared with those in the control group; of these, MALAT1and NEAT1 were screened and validated using RT-qPCR. Common NSCL/P risk factors positively correlated with MALAT1 and NEAT1 expression (ORMALAT1 = 28.111, 95% CI: 4.054-194.923; ORNEAT1 = 30.556, 95% CI: 4.422-211.142; P < 0.05). Bioinformatics predicted four ceRNA networks: MALAT1-hsa-miR-1224-3p-SP1, MALAT1-hsa-miR-6734-5p/hsa-miR-1224-3p-WNT10A, NEAT1-hsa-miR-140-3p.1-CXCR4, and NEAT1-hsa-miR-3129-5p/hsa-miR-199a-3p/hsa-miR-199b-3p-ZEB1. GO enrichment focused on the potential functions of ceRNA networks, including biosynthesis of organic cyclic compounds, formation of membrane-enclosed and organelle lumens, and Wnt-protein binding. The results of RT-qPCR were consistent with those of IHC staining with regard to expression of related mRNAs. MALAT1 and NEAT1, which are upregulated in NSCL/P, are associated with the severity of NSCL/P. This study provides a new insight into NSCL/P pathogenesis and suggests that MALAT1 and NEAT1 act as potential therapeutic targets and prognostic biomarkers for NSCL/P.
2021-09-07 | GSE183527 | GEO
Project description:Long noncoding RNAs (lncRNAs) are important regulators of chromatin; however, the mechanistic roles for many lncRNAs are poorly understood in part because their direct interactions with genomic loci and proteins are difficult to assess. We used CHART-seq to map the genomic binding sites for two highly expressed human lncRNAs, NEAT1 and MALAT1, which localize within the nucleus to paraspeckles and nuclear speckles, respectively. We show that NEAT1 and MALAT1 localize to hundreds of genomic sites in human cells, primarily over active genes. NEAT1 and MALAT1 exhibit colocalization to many of these loci, but display distinct gene body binding patterns at these sites, suggesting independent but complementary functions for these RNAs. Protein mass spectrometry analysis of CHART-enriched material (CHART-MS) identified numerous proteins enriched by both lncRNAs, supporting complementary binding and function, in addition to unique associated proteins. Transcriptional inhibition or stimulation affects the localization of NEAT1 to active chromatin sites, implying that DNA sequence itself does not target NEAT1 to chromatin and that localization responds to cues involved in the transcription process. Paired-end CHART-seq was performed for a single replicate of each capture oligonucleotide in untreated MCF-7 cells to establish binding sites of these RNAs, for a total of 6 samples. To investigate the effects of transcriptional inhibition and E2 stimulation on the localization of these RNAs, we performed paired-end CHART-seq with each capture oligonucleotide for two biological replicates of flavopiridol- and vehicle (DMSO)-treated MCF-7 cells and for two biological replicates of E2- and vehicle (ethanol)-treated MCF-7 cells. To establish the overlap of NEAT1 and MALAT1 binding sites with a known component of paraspeckles (NEAT1-containing subnuclear body), we performed paired-end ChIP-seq for the paraspeckle component PSF in MCF-7 cells, as well as a single-end biological replicate.
2014-08-12 | E-GEOD-58444 | biostudies-arrayexpress