Expression signatures of long non-coding RNAs and mRNAs in lung tissues in obesity and obesity-related acute lung injury
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA953764 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:This result is expected to identify several lncRNAs and mRNAs that are dysregulated in the lung due to obesity, as well as obesity-associated lncRNAs and mRNAs that are further altered in acute lung injury, as biomarkers specific to obesity-associated acute lung injury. To provide useful information for elucidating the development of acute lung injury exacerbated by obesity and exploring potential therapeutic targets
2024-01-30 | GSE229262 | GEO
Project description:Long non-coding RNAs are closely associated with the regulation of various biological processes and are involved in the pathogenesis of numerous diseases. However, the role of lncRNAs in ventilator-induced lung injury (VILI) has yet to be evaluated. This study aims to evaluate the expression profile and role of lncRNAs and mRNAs in VILI.
2021-05-07 | GSE114132 | GEO
Project description:Long non-coding RNAs (lncRNAs) are involved in various biological processes as well as many respiratory diseases, while the role of lncRNAs in acute lung injury (ALI) remains unclear. The present study aimed to profile the expression of lung lncRNAs and mRNAs in lipopolysaccharide (LPS)-induced ALI mouse model. C57BL/6 mice were exposed to LPS or phosphate-buffered saline for 24 h, and lncRNAs and mRNAs were profiled by Arraystar mouse LncRNA Array V3.0. Bioinformatics analysis gene ontology including (GO) and pathway analysis and cell study in vitro was used to investigate potential mechanisms. Based on the microarray results, 2632 lncRNAs and 2352 mRNAs were differentially expressed between ALI and control mice. The microarray results were confirmed by the quantitative real-time PCR (qRT-PCR) results of ten randomized selected lncRNAs. GO analysis showed that the altered mRNAs were mainly related to the processes of immune system, immune response and defense response. Pathway analysis suggests that tumor necrosis factor (TNF) signaling pathway, NOD-like receptor pathway, and cytokine-cytokine receptor interaction may be involved in ALI. LncRNA-mRNA co-expression network analysis indicated that one individual lncRNA may interact with several mRNAs, and one individual mRNA may also interact with several lncRNAs. Small interfering RNA (siRNA) for ENSMUST00000170214.1, - ENSMUST00000016031.13 significantly inhibited LPS-induced TNF-α and interleukin (IL)-1β production in murine RAW264.7 macrophages. Our results found significant changes of lncRNAs and mRNAs in the lungs of LPS-induced ALI mouse model, and intervention targeting lncRNAs may attenuate LPS-induced inflammation, which may help to elucidate the role of lncRNAs in the pathogenesis and treatment of ALI.
| S-EPMC6488857 | biostudies-literature
Project description:Background: Obesity has become a worldwide concern. Acute respiratory distress syndrome (ARDS) comprises 10.4% of total intensive care unit admissions and is associated with very high mortality. ARDS incidence is increased in obese patients. Exposure of rodents to hyperoxia mimics many of the clinical and pathologic features observed in patients with ARDS. The aim of this study was to determine the impact of high fat diet-induced obesity on the susceptibility to hyperoxic acute lung injury in mice. Methods: Male C57BL/6 mice received 60% fat versus ingredient matched 10% fat diet. Mice were exposed to >95% oxygen to induce lung damage. RNA was isolated from lung homogenates and by comparing RNA sequencing results with mouse Mitocarta, an inventory of genes encoding proteins with mitochondrial localization, we identified fatty acid synthase (FASN), an enzyme catalyzing de novo fatty acid synthesis, as one of the mitochondrial genes significantly changed with diet and with hyperoxia. We generated mice deficient in FASN in alveolar epithelial cells by using a tamoxifen inducible Cre recombinase construct (FASNflox/flox SPC Cre+/-) and subjected them to hyperoxia and high fat diet. Results: Mice receiving 60% fat diet had significantly higher weight, serum cholesterol and fasting glucose. High fat diet mice had significantly reduced survival and increased lung damage, as assessed by BAL protein and LDH, histology and TUNEL staining. By RNA sequencing of lung homogenates we identified FASN as one of the mitochondrial genes significantly reduced in mice receiving 60% compared to 10% fat diet and further reduced with hyperoxia. We confirmed that FASN protein levels in the lung of high fat diet mice were lower by immunoblotting and immunohistochemistry. After 48 hours of hyperoxia FASNflox/flox SPC Cre+/- mice displayed increased levels of BAL protein and LDH and more severe histologic lung injury. FASNflox/flox SPC Cre+/- mice remained more prone to lung injury after hyperoxic exposure even when they received 60% fat diet. Conclusions: These results demonstrate that obesity increases the severity of hyperoxia induced acute lung injury in mice by altering FASN levels in the lung of high fat diet fed rodents. To our knowledge, this is the first study to show that high fat diet leads to altered FASN expression in the lung and that both high fat diet and reduced FASN in alveolar epithelial cells lead to increased lung injury under hyperoxic conditions.
2019-07-25 | GSE123938 | GEO
Project description:Impact of Diet Induced Obesity on Hyperoxic Lung Injury
| PRJNA510361 | ENA
Project description:Effect of obesity on mouse lung transcriptome
| PRJEB57780 | ENA
Project description:Long non-coding RNAs (lncRNAs) are closely associated with the regulation of various biological processes and are involved in the pathogenesis of numerous diseases. However, to the best of our knowledge, the role of lncRNAs in ventilator?induced lung injury (VILI) has yet to be evaluated. In the present study, high?throughput sequencing was applied to investigate differentially expressed lncRNAs and mRNAs (fold change >2; false discovery rate <0.05). Bioinformatics analysis was employed to predict the functions of differentially expressed lncRNAs. A total of 104 lncRNAs (74 upregulated and 30 downregulated) and 809 mRNAs (521 upregulated and 288 downregulated) were differentially expressed in lung tissues from the VILI group. Gene ontology analysis demonstrated that the differentially expressed lncRNAs and mRNAs were mainly associated with biological functions, including apoptosis, angiogenesis, neutrophil chemotaxis and skeletal muscle cell differentiation. The top four enriched pathways were the tumor necrosis factor (TNF) signaling pathway, P53 signaling pathway, neuroactive ligand?receptor interaction and the forkhead box O signaling pathway. Several lncRNAs were predicted to serve a vital role in VILI. Subsequently, three lncRNAs [mitogen?activated protein kinase kinase 3, opposite strand (Map2k3os), dynamin 3, opposite strand and abhydrolase domain containing 11, opposite strand] and three mRNAs (growth arrest and DNA damage?inducible ?, claudin 4 and thromboxane A2 receptor) were measured by reverse transcription?quantitative polymerase chain reaction, in order to confirm the veracity of RNA?sequencing analysis. In addition, Map2k3os small interfering RNA transfection inhibited the expression of stretch?induced cytokines [TNF??, interleukin (IL)?1? and IL?6] in MLE12 cells. In conclusion, the results of the present study provided a profile of differentially expressed lncRNAs in VILI. Several important lncRNAs may be involved in the pathological process of VILI, which may be useful to guide further investigation into the pathogenesis for this disease.
| S-EPMC6059720 | biostudies-literature
Project description:Daidzein has been found to significantly inhibit the proliferation of lung cancer cells, while its potential molecular mechanisms remain unclear. To determine the molecular mechanism of daidzein on lung cancer cells, the Capital Bio Technology Human long non-coding (lnc)RNA Array v4, 4x180K chip was used to detect the gene expression profiles of 40,000 lncRNAs and 34,000 mRNAs in a human cancer cell line. Reverse transcription-quantitative (RT-q) PCR analysis was performed to detect the expression levels of target lncRNA and mRNAs in the H1299 cells treated with and without daidzein, using the lncRNA and mRNA gene chip. Bioinformatics analysis was performed to determine the differentially expressed genes from the results of the chip assays. There were 119 and 40 differentially expressed lncRNAs and mRNAs, respectively, that had a 2-fold change in expression level. A total of eight lncRNAs were upregulated in the H1299 lung cancer cells, while 111 lncRNAs were downregulated. Furthermore, five mRNAs were upregulated, and 35 mRNAs were downregulated. A total of six differentially expressed lncRNAs (ENST00000608897.1, ENST00000444196.1, ENST00000608741.1, XR_242163.1, ENST00000505196.1 and ENST00000498032.1) were randomly selected to validate the microarray data, which were consistent with the RT-qPCR analysis results. Differentially expressed mRNAs were enriched in important Gene Ontology terms and Kyoto Encyclopedia of Genes and Genomes pathways. Taken together, the results of the present study demonstrated that daidzein affected the expression level of lncRNAs in lung cancer cells, suggesting that daidzein may have potential effects on lung cancer cells.
2021-08-05 | GSE181093 | GEO
Project description:BackgroundLung adenocarcinoma (LUAD), largely remains a primary cause of cancer-related death worldwide. The molecular mechanisms in LUAD metastasis have not been completely uncovered.MethodsIn this study, we identified differentially expressed genes (DEGs), miRNAs (DEMs) and lncRNAs (DELs) underlying metastasis of LUAD from The Cancer Genome Atlas database. Intersection mRNAs were used to perform gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and co-expression network analysis. In addition, survival analyses of intersection mRNAs were conducted. Finally, intersection mRNAs, miRNAs and lncRNAs were subjected to construct miRNA-mRNA-lncRNA network.ResultsA total of 1015 DEGs, 54 DEMs and 22 DELs were identified in LUAD metastasis and non-metastasis samples. GO and KEGG pathway analysis had proven that the functions of intersection mRNAs were closely related with many important processes in cancer pathogenesis. Among the co-expression interactions network, 22 genes in the co-expression network were over the degree 20. These genes imply that they have connections with many other gene nodes. In addition, 14 target genes (ARHGAP11A, ASPM, HELLS, PRC1, TMPO, ARHGAP30, CD52, IL16, IRF8, P2RY13, PRKCB, PTPRC, SASH3 and TRAF3IP3) were found to be associated with survival in patients with LUAD significantly (log-rank P?<?0.05). Two lncRNAs (LOC96610 and ADAM6) acting as ceRNAs were identified based on the miRNA-mRNA-lncRNA network.ConclusionsTaken together, the results may provide a novel perspective to develop a multiple gene diagnostic tool for LUAD prognosis, which might also provide potential biomarkers or therapeutic targets for LUAD.
| S-EPMC6307237 | biostudies-literature
Project description:Lung adenocarcinoma (LUAD) is the primary subtype in lung cancer, which is the leading cause of cancer-related death worldwide. This study aimed to investigate the aberrant expression profiling of long non-coding RNA (lncRNA) in TNM I stage (stage I) LUAD. The lncRNA/mRNA/miRNA expression profiling of stage I LUAD and adjacent non-tumor tissues from 4 patients were measured by RNA-sequencing. Total of 175 differentially expressed lncRNAs (DELs), 1321 differentially expressed mRNAs (DEMs) and 94 differentially expressed microRNAs (DEMIs) were identified in stage I LUAD. DEMI-DEM regulatory network consisted of 544 nodes and 1123 edge; miR-200 family members had high connectivity with DEMs. In DEL-DEM co-expression network, CDKN2B-AS1, FENDRR and LINC00312 had the high connectivity with DEMs, which co-expressed with 105, 63 and 61 DEMs, respectively. DEL-DEMI-DEM network depicted the links among DELs, DEMI and DEMs. Identified DEMs were significantly enriched in cell adhesion molecules, focal adhesion and tight junction of Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways; and enriched in cell adhesion, angiogenesis and regulation of cell proliferation of Gene Ontology biological processes. Quantitative real-time polymerase chain reaction results were generally consistent with our bioinformatics analyses. LINC00312 and FENDRR had diagnostic value for LUAD patients in The Cancer Genome Atlas database. Our study might lay the foundation for illumination of pathogenesis of LUAD and identification of potential therapeutic targets and novel diagnosis biomarkers for LUAD patients.
| S-EPMC5584281 | biostudies-literature