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Comprehensive Analysis of Potential ceRNA Network and Different Degrees of Immune Cell Infiltration in Acute Respiratory Distress Syndrome.

ABSTRACT: Acute respiratory distress syndrome (ARDS) is a leading cause of death in critically ill patients due to hypoxemic respiratory failure. The specific pathogenesis underlying ARDS has not been fully elucidated. In this study, we constructed a triple regulatory network involving competing endogenous RNA (ceRNA) to investigate the potential mechanism of ARDS and evaluated the immune cell infiltration patterns in ARDS patients. Overall, we downloaded three microarray datasets that included 60 patients with sepsis-induced ARDS and 79 patients with sepsis alone from the public Gene Expression Omnibus (GEO) database and identified differentially expressed genes (DEGs, including 9 DElncRNAs, 9 DEmiRNAs, and 269 DEmRNAs) by R software. The DEGs were subjected to the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) for functional enrichment analysis, and a protein-protein interaction (PPI) network was generated for uncovering interactive relationships among DEmRNAs. Then, a ceRNA network that contained 5 DElncRNAs, 7 DEmiRNAs, and 71 DEmRNAs was established according to the overlapping genes in both DEGs and predicted genes by public databases. Finally, we identified the TUG1/miR-140-5p/NFE2L2 pathway as the hub pathway in the whole network through Cytoscape. In addition, we evaluated the distribution of 22 subtypes of immune cells and recognized three differentially expressed immune cells in patients with sepsis-induced ARDS by "Cell Type Identification by Estimating Relative Subsets of Known RNA Transcripts (CIBERSORT)" algorithm, namely, naive B cells, regulatory T cells, and eosinophils. Correlations between differentially expressed immune cells and hub genes in the ceRNA network were also performed. In conclusion, we demonstrated a new potential regulatory mechanism underlying ARDS (the TUG1/miR-140-5p/NFE2L2 ceRNA regulatory pathway), which may help in further exploring the pathogenesis of ARDS.

SUBMITTER: Hu J

PROVIDER: S-EPMC9198558 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background: Increasing evidence supports that competing endogenous RNAs (ceRNAs) and tumor immune infiltration act as pivotal players in tumor progression of hepatocellular carcinoma (HCC). Nonetheless, comprehensive analysis focusing on ceRNAs and immune infiltration in HCC is lacking. Methods: RNA and miRNA sequencing information, corresponding clinical annotation, and mutation data of HCC downloaded from The Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-LIHC) project were employed to identify significant differentially expressed mRNAs (DEMs), miRNAs (DEMis), and lncRNAs (DELs) to establish a ceRNA regulatory network. The Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene ontology (GO) enrichment pathways were analyzed to functionally annotate these DEMs. A multigene-based risk signature was developed utilizing least absolute shrinkage and selection operator method (LASSO) algorithm. Moreover, survival analysis and receiver operating characteristic (ROC) analysis were applied for prognostic value validation. Seven algorithms (TIMER, XCELL, MCPcounter, QUANTISEQ, CIBERSORT, EPIC, and CIBERSORT-ABS) were utilized to characterize tumor immune microenvironment (TIME). Finally, the mutation data were analyzed by employing "maftools" package. Results: In total, 136 DELs, 128 DEMis, and 2,028 DEMs were recognized in HCC. A specific lncRNA-miRNA-mRNA network consisting of 3 lncRNAs, 12 miRNAs, and 21 mRNAs was established. A ceRNA-based prognostic signature was established to classify samples into two risk subgroups, which presented excellent prognostic performance. In additional, prognostic risk-clinical nomogram was delineated to assess risk of individual sample quantitatively. Besides, risk score was significantly associated with contexture of TIME and immunotherapeutic targets. Finally, potential interaction between risk score with tumor mutation burden (TMB) was revealed. Conclusion: In this work, comprehensive analyses of ceRNAs coexpression network will facilitate prognostic prediction, delineate complexity of TIME, and contribute insight into precision therapy for HCC.

Project description:BackgroundOur previous studies have confirmed that miR-154-5p can regulate pRb expression, and thus, play a tumor suppressor role in HPV16 E7-induced cervical cancer. However, its upstream molecules have not been elucidated in the progression of cervical cancer. This study aimed to explore the role of the miR-154-5p upstream molecule, hsa_circ_0000276 in cervical cancer development and its possible mechanisms of action.MethodsWe detected differences in whole transcriptome expression profiles of cervical squamous carcinoma and tissues adjacent to cervical cancer tissues from patients using microarray technology to predict circular RNAs (circRNAs) with binding sites to miR-154-5p. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to detect the expression of hsa_circ_0000276 (which had the strongest binding capacity to miR-154 and was selected as the target molecule) in cervical cancer tissues, followed by in vitro functional assays. Downstream microRNAs (miRNAs) and mRNAs of hsa_circ_0000276 were identified using transcriptome microarray data and databases, while the protein-protein interaction networks were obtained using STRING. A competing endogenous RNA (ceRNA) network centered on hsa_circ_0000276 was constructed using Cytoscape and GO and KEGG databases. Abnormal expression and prognosis of critical downstream molecules were analyzed using gene databases and molecular experiments. qRT-PCR and western blot analysis was performed to verify the expression of candidate genes.ResultsWe identified 4,001 differentially expressed circRNAs between HPV16-positive cervical squamous carcinoma and benign cervical tissues and 760 circRNAs targeting miR-154-5p, including hsa_circ_0000276. hsa_circ_0000276 and miR-154-5p directly bound, and hsa_circ_0000276 was upregulated, in cervical precancerous lesions and cervical cancer tissues and cells. Silencing hsa_circ_0000276 inhibited G1/S transition and cell proliferation and promoted apoptosis in SiHa and CaSki cells. Bioinformatics analysis showed that the hsa_circ_0000276 ceRNA network included 17 miRNAs and seven mRNAs, and downstream molecules of hsa_circ_0000276 were upregulated in cervical cancer tissues. These downstream molecules were associated with a poor prognosis and affected cervical cancer-associated immune infiltration. Of these, expression of CD47, LDHA, PDIA3, and SLC16A1 was downregulated in sh_hsa_circ_0000276 cells.ConclusionsOur findings show that hsa_circ_0000276 exerts cancer-promoting effects in cervical cancer and is an underlying biomarker for cervical squamous cell carcinoma.

Project description:Purpose: Kidney stones is a common medical issue that mediates kidney injury and even kidney function loss. However, the exact pathogenesis still remains unclear. This study aimed to explore the potential competing endogenous RNA (ceRNA)-related pathogenesis of kidney stones and identify the corresponding immune infiltration signature. Methods: One mRNA and one long non-coding RNA (lncRNA) microarray dataset was obtained from the GEO database. Subsequently, we compared differentially expressed mRNAs (DE-mRNAs) and lncRNAs between Randall's plaques in patients with calcium oxalate (CaOx) stones and controls with normal papillary tissues. lncRNA-targeted miRNAs and miRNA-mRNA pairs were predicted using the online databases. lncRNA-related DE-mRNAs were identified using the Venn method, and GO and KEGG enrichment analyses were subsequently performed. The immune-related lncRNA-miRNA-mRNA ceRNA network was developed. The CIBERSORT algorithm was used to estimate the rate of immune cell infiltration in Randall's plaques. The ceRNA network and immune infiltration were validated in the glyoxylate-induced hyperoxaluric mouse model and oxalate-treated HK-2 cells. Results: We identified 2,340 DE-mRNAs and 929 DE-lncRNAs between Randall's plaques in patients with CaOx stones and controls with normal papillary tissues. lncRNA-related DE-mRNAs were significantly enriched in extracellular matrix organization and collagen-containing extracellular matrix, which were associated with kidney interstitial fibrosis. The immune-related ceRNA network included 10 lncRNAs, 23 miRNAs, and 20 mRNAs. Moreover, we found that M2 macrophages and resting mast cells were differentially expressed between Randall's plaques and normal tissues. Throughout kidney stone development, kidney tubular injury, crystal deposition, collagen fiber deposition, TGF-β expression, infiltration of M1 macrophages, and activation of mast cells were more frequent in glyoxylate-induced hyperoxaluric mice compared with control mice. Nevertheless, M2 macrophage infiltration increased in early stages (day 6) and decreased as kidney stones progressed (day 12). Furthermore, treatment with 0.25 and 0.5 mM of oxalate for 48 h significantly upregulated NEAT1, PVT1, CCL7, and ROBO2 expression levels and downregulated hsa-miR-23b-3p, hsa-miR-429, and hsa-miR-139-5p expression levels in the HK-2 cell line in a dose-dependent manner. Conclusion: We found that significant expressions of ceRNAs (NEAT1, PVT1, hsa-miR-23b-3p, hsa-miR-429, hsa-miR-139-5p, CCL7, and ROBO2) and infiltrating immune cells (macrophages and mast cells) may be involved in kidney stone pathogenesis. These findings provide novel potential therapeutic targets for kidney stones.

Project description:BackgroundBladder cancer (BC) is the ninth most common malignant tumor, accounting for an estimate of 549,000 new BC cases and 200,000 BC-related deaths worldwide in 2018. The prognosis of BC has not substantially improved despite significant advances in the diagnosis and treatment of the disease.MethodsThe RNA sequencing (RNA-seq) data and clinical information of BC patients were downloaded from The Cancer Genome Atlas (TCGA) database. The Cell-type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT) algorithm was used to assess immune infiltration. The survival analyses were performed using the selected components of a ceRNA network and selected immune cell types by least absolute shrinkage and selection operator (LASSO) Cox regression to calculate the risk score. The accuracy of prognosis prediction was determined by receiver operating characteristic (ROC) curves, survival curves, and nomograms. Finally, the correlation analysis was performed to investigate the relationships between the signature components of the ceRNA network and the immune cell signature.ResultsTwo completed survival analyses included selected components of the ceRNA network (ELN, SREBF1, DSC2, TTLL7, DIP2C, SATB1, hsa-miR-20a-5p, and hsa-miR-29c-3p) and selected immune cell types (M0 macrophages, M2 macrophages, resting mast cells, and neutrophils). ROC curves, survival curves (all P values <0.05), nomograms, and calibration curves indicated that the accuracy of the two survival analyses was acceptable. Moreover, the correlations between TTLL7 and resting mast cells (R=0.24, P<0.001), DSC2 and resting mast cells (R=-0.23, P<0.001), ELN and resting mast cells (R=0.44, P<0.001), and hsa-miR-29c-3p and M0 macrophages (R=-0.29, P<0.001) were significant, indicating that interactions of these factors may play significant roles in the prognosis of BC.ConclusionsTTLL7, DSC2, ELN, hsa-miR-29c-3p, resting mast cells, and M0 macrophages may play an important role in the development of BC. However, additional studies are needed to confirm this hypothesis.

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Comprehensive Analysis of Potential ceRNA Network and Different Degrees of Immune Cell Infiltration in Acute Respiratory Distress Syndrome.

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