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Whole transcriptome sequencing explored the toxic effect of cadmiun on Caenorhabditis elegans [RNA-seq]

ABSTRACT: Purpose: Cadmium (Cd) is detrimental to environment and human health, but the specific mechanism of the regulatory network is still remained unclear. Caenorhabditis elegans (C. elegans) is selected as the ideal model organism to investigate the effect of Cd exposure. Methods: We employed the phosphoproteomic technologies, high-throughput sequencing method and bioinformatic tools (RNAhybrid, Risearch2 and Targetscan) to investigate the phosphorylated change and the regulatory networks of circRNA, lncRNA, microRNA (miRNA) and mRNA after Cd exposure in C. elegans. The Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene set enrichment analysis (GSEA) were also employed. The relationship between transcriptional factors (TFs) and kinases, and the kinase-substrate were predicted using Jaspar database and iGPS, respectively. Results:26 differentially expressed circRNAs (DEcircRNAs), 143 lncRNAs (DElncRNAs), 69 miRNAs (DEmiRNAs) and 6209 mRNAs (DEmRNAs) were identified. According to qRCR, four DEcircRNAs and three DElncRNAs were found and confirmed the different expression levels between the treated and control group. 23 miRNAs and six miRNAs were the potential targets of the confirmed circRNAs and lncRNAs respectively using the predictive tools of RNAhybrid, RIsearch and Targetscan. Similarly, the target mRNAs of miRNAs were identified. Next, the regulatory network of lncRNA-miRNA-mRNA and circRNA-miRNA-mRNA were established. Furthermore, five protein-coding genes might be regulated by DElnRNAs through cis-acting and 114 by trans-acting. The GO and KEGG analysis were performing on the parents’ genes of the mRNAs. GSEA was performed on all protein-coding genes, and the correlation between these genes and validated lncRNAs were used for pre-ranking. For the phosphopromotics, 42 differentially regulative phosphopeptides were identified. In this work, four novel pairs of TFs-kinases-substrate which might be influenced by Cd exposure were firstly constructed. Conclusions: Cd might mainly influence the reproductive function and aging of C. elegans through regulating the circRNAs and lncRNAs. Also, it might inhibit the expression of TFs to reduce the phosphorylated level of corresponding protein.

ORGANISM(S): Caenorhabditis elegans

PROVIDER: GSE189660 | GEO | 2024/11/24

REPOSITORIES: GEO

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Project description:Purpose: Cadmium (Cd) is detrimental to environment and human health, but the specific mechanism of the regulatory network is still remained unclear. Caenorhabditis elegans (C. elegans) is selected as the ideal model organism to investigate the effect of Cd exposure. Methods: We employed the phosphoproteomic technologies, high-throughput sequencing method and bioinformatic tools (RNAhybrid, Risearch2 and Targetscan) to investigate the phosphorylated change and the regulatory networks of circRNA, lncRNA, microRNA (miRNA) and mRNA after Cd exposure in C. elegans. The Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene set enrichment analysis (GSEA) were also employed. The relationship between transcriptional factors (TFs) and kinases, and the kinase-substrate were predicted using Jaspar database and iGPS, respectively. Results:26 differentially expressed circRNAs (DEcircRNAs), 143 lncRNAs (DElncRNAs), 69 miRNAs (DEmiRNAs) and 6209 mRNAs (DEmRNAs) were identified. According to qRCR, four DEcircRNAs and three DElncRNAs were found and confirmed the different expression levels between the treated and control group. 23 miRNAs and six miRNAs were the potential targets of the confirmed circRNAs and lncRNAs respectively using the predictive tools of RNAhybrid, RIsearch and Targetscan. Similarly, the target mRNAs of miRNAs were identified. Next, the regulatory network of lncRNA-miRNA-mRNA and circRNA-miRNA-mRNA were established. Furthermore, five protein-coding genes might be regulated by DElnRNAs through cis-acting and 114 by trans-acting. The GO and KEGG analysis were performing on the parents’ genes of the mRNAs. GSEA was performed on all protein-coding genes, and the correlation between these genes and validated lncRNAs were used for pre-ranking. For the phosphopromotics, 42 differentially regulative phosphopeptides were identified. In this work, four novel pairs of TFs-kinases-substrate which might be influenced by Cd exposure were firstly constructed. Conclusions: Cd might mainly influence the reproductive function and aging of C. elegans through regulating the circRNAs and lncRNAs. Also, it might inhibit the expression of TFs to reduce the phosphorylated level of corresponding protein.

Project description:Background and aims: Aortic dissection (AD) is a cardiovascular emergency with degeneration of the aortic media. Mounting evidence indicates obstructive sleep apnea (OSA) as an independent risk factor for AD development with unknown mechanisms. This study aims to establish a stable murine model of OSA-related AD (OSA-AD) and uncover the potential changes in gene transcripts in OSA-AD. Materials and methods: ApoE-/- mice were exposed to the chronic intermittent hypoxia (CIH) system combined with Ang II administration to establish the OSA-AD model. Pathological staining was performed to exhibit the physiological structure of the mouse aorta. The SBC mouse ceRNA microarray was used to identify significantly differentially expressed (DE) mRNAs, DE long-non-coding RNAs (DElncRNAs), and DE circular RNAs (DEcircRNAs) in OSA-AD tissues. Subsequently, bioinformatics analysis, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genome (KEGG), and protein–protein interaction (PPI) analyses, was performed to evaluate the function of the significantly differentially expressed transcripts (DETs). The hub genes were confirmed using quantitative real-time polymerase chain reaction (qRT-PCR). Results: ApoE-/- mice exposed to CIH and Ang II showed a high ratio of aortic accident (73.33%) and significant aortic diameter dilatation (1.96 ± 0.175 mm). A total of 1,742 mRNAs, 2,625 lncRNAs, and 537 circRNAs were identified as DETs (LogFC ≥ 1.5 or ≤ –1.5, P < 0.05). GO and KEGG analyses demonstrated that the differentially expressed mRNAs (DEmRNAs) were most enriched in cell proliferation, migration, apoptosis, inflammation, and hypoxia-related terms, which are closely related to aortic structural homeostasis. The PPI network contained 609 nodes and 934 connections, the hub genes were highlighted with the CytoHubba plugin and confirmed by qRT-PCR in AD tissues. KEGG pathway analysis revealed that the cis-regulated genes of DElncRNAs and circRNAs-host genes were enriched in aortic structural homeostasis-related pathways. Conclusion: Our findings help establish a de novo OSA-AD animal model using ApoE-/- mice. Many DEmRNAs, DElncRNAs, and DEcircRNAs were screened for the first time in OSA-AD tissues. Our findings provide useful bioinformatics data for understanding the molecular mechanism of OSA-AD and developing potential therapeutic strategies for OSA-AD.

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Whole transcriptome sequencing explored the toxic effect of cadmiun on Caenorhabditis elegans [RNA-seq]

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