Integrated analysis of high-throughput sequencing-based lncRNA-mediated ceRNA network in Hepatic Alveolar Echinococcosis
Zhen, L.; Chang-zhen, S.; Jin-peng, W.; Zhi-gang, G.; Fu-cai, M.; Pan, X.; Yan, W.; Xiao, Y.; Hai-hong, Z.
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BackgroundNumerous studies have indicated that long non-coding RNAs (lncRNAs) can modulate the expression of target gene mRNAs by adsorbing microRNAs (miRNAs). The lncRNA-miRNA-mRNA ceRNA network has been theorized to play an indispensable role in many types of tumors, and has been garnering increasing attention. However, the role of the lncRNA-associated ceRNA regulatory network in Hepatic Alveolar Echinococcosis (HAE) remains unclear and requires further exploration. MethodsIn this study, high-throughput sequencing was performed on lesion tissues and adjacent tissues from three patients with Hepatic Alveolar Echinococcosis (HAE) to identify differentially expressed RNAs. We utilized Cytoscape (version 3.10.1) to construct the lncRNA-miRNA-mRNA ceRNA network based on the interactions from the miRcode, miRTarBase, miRDB, and TargetScan databases, and identified hub lncRNAs from within the ceRNA network. Through the use of the "clusterProfiler" package in R, we performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotations for the DEGs (Differentially Expressed Genes) within the ceRNA network. Concurrently, we utilized these DEGs to construct a protein-protein interaction network (PPI). Finally, an analysis was conducted on the PCBP1-AS1-miR-20b-5p/CAPRIN2 axis within the ceRNA network. ResultsIn HAE, a total of 979 differentially expressed lncRNAs (DELncRNAs) and 870 differentially expressed mRNAs (DEmRNAs) were identified. An HAE-specific ceRNA network comprising 11 lncRNAs, 21 miRNAs, and 56 mRNAs was established, and analysis of this network led to the construction of a sub-network associated with hub lncRNAs. GO and KEGG pathway analyses indicated that the HAE-specific ceRNA network is related to molecular functions and pathways associated with cancer. Subsequent experiments using qPCR and dual-luciferase assays validated the interactions between PCBP1-AS1 and miR-20b-5p, as well as between miR-20b-5p and CAPRIN2. Analysis of the target gene in relation to clinical characteristics of HAE patients suggested that the PCBP1-AS1-miR-20b-5p/CAPRIN2 axis may influence the development of HAE. ConclusionIn this study, we described the gene regulation within the lncRNA-miRNA-mRNA ceRNA network during the development of Hepatic Alveolar Echinococcosis (HAE), which contributes to a deeper exploration of the molecular mechanisms underlying HAE. Additionally, we discovered that PCBP1-AS1 may regulate the expression of CAPRIN2 by adsorbing miR-20b-5p, affecting the onset and progression of HAE. PCBP1-AS1 could potentially serve as a useful target for the diagnosis and treatment of HAE.
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