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Environmental cadmium-induced circRNA-miRNA-mRNA network regulatory mechanism in human normal liver cell model [circRNA]

ABSTRACT: Cadmium is a naturally existing heavy metal and a typical environmental pollutant which is a significant threat to human health and can lead to acute and chronic damage to various organs. At present, hundreds of lncRNAs and miRNAs have been confirmed to be related to the toxicity of Cd. However, the role of circRNA in the toxicity of Cd and the involved regulatory mechanism has not been clarified. In this work, human normal liver cell (L-02) was selected as model to identify the changes in the expression level of circRNA after exposure to Cd. Total RNA of each sample was extracted by Trizol method, the original data of circRNA, miRNA and mRNA expression levels of each sample were obtained by microarray hybridization and scanning were standardized and differentially expressed. Differential circRNAs, miRNAs, and mRNAs associated with the toxic effects of Cd were identified. Construct a ceRNA network by screening the predicted circRNA, miRNA and mRNA and predict the main biological functions and metabolic pathways of the network. A total of 266 different circRNAs, 223 different miRNAs and 519 different mRNAs were identified by differential expression analysis. After screening, seven circRNAs, 10 miRNAs and 97 mRNAs were constructed into ceRNA network. After GO enrichment and KEGG pathway analysis of 97 mRNAs in circRNA-miRNA-mRNA network, indicated that circRNA in the ceRNA network may regulate cell proliferation, apoptosis, oxidative stress and inflammatory response under the toxic effect of Cd to damage L-02, and it has obvious dose-response effect and time effect.

ORGANISM(S): Homo sapiens

PROVIDER: GSE246129 | GEO | 2024/10/08

REPOSITORIES: GEO

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Project description:Background: There is growing evidence that circular RNAs (circRNAs) play an important role in a variety of diseases, including erectile dysfunction (ED). Nevertheless, the role of circRNAs in cavernous nerve-damaging ED (CNI-ED) is unknown. Here, we aimed to discover new circRNAs, investigate their potential role in the pathogenesis of CNI-ED, and construct a circRNA-miRNA-mRNA network. Methods: Twelve male Sprague Dawley rats were randomly divided into bilateral cavernous nerve crush (BCNC) and control groups. Four weeks after surgery, the spongy smooth muscle tissue of the rat penis was sequenced using high-throughput full transcriptome sequencing. We analyzed the expression profiles of circRNAs, miRNAs, and mRNAs in the two groups. Twenty circRNAs with significantly different expressions were selected for real-time polymerase chain reaction (RT-qPCR). The circRNA-miRNA-mRNA network was established using Cytoscape. Gene ontology (GO)-term and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed using the edgeR package. Results: RNA transcriptome sequencing showed that 4,587 circRNAs, 762 miRNAs, and 21,661 mRNAs were dysregulated in the BCNC group. The top 20 differentially expressed circRNAs were further verified via RT-qPCR. The ceRNA network contained 23 circRNA-miRNA pairs and 227 miRNA-mRNA pairs, including ten circRNAs, six miRNAs, and 227 mRNAs. GO analysis suggested that these ten circRNAs could regulate various processes, such as oxidation-reduction processes, lipid metabolic processes, apoptotic processes, and proteolysis. Furthermore, KEGG analysis of mRNAs in the ceRNA network showed that they were involved in energy metabolism and communication between cells. A protein‐protein interaction network was constructed with the 227 mRNAs, and five hub genes (Ccna2, Cxcl10, Pld1, Mapk11, and Mboat2) were identified. In addition, Using circRNADb, we found 12 circRNAs with protein-coding potential, three of which were highly conserved in humans and rats. Our study revealed a potential link between circRNAs, miRNAs, and mRNAs in CNI-ED, suggesting that circRNAs may contribute to the occurrence of ED by regulating the cellular energy metabolism in CNI-ED.

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Environmental cadmium-induced circRNA-miRNA-mRNA network regulatory mechanism in human normal liver cell model [circRNA]

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