Bioinformatics analysis of long non-coding RNA-associated competing endogenous RNA network in hepatoblastoma

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Abstract Hepatoblastoma (HB) is a common pediatric hepatic tumor. Occurrence and progression of various malignancies are enhanced by abnormal competitive endogenous RNA (ceRNA) axes. Although, ceRNAs can be considered effective prognostic, diagnostic, and therapeutic targets, it is poorly investigated in HB. An lncRNA-related ceRNA network is developed in the current study to clarify HB's underlying molecular regulatory mechanism. First, two microarray datasets regarding the liver specimens of HB patients and controls were downloaded from Gene Expression Omnibus database, which contained mRNAs, lncRNAs (GSE75271), and miRNAs (GSE75283) data. R software package limma was used to identify the differentially expressed lncRNAs (DElncRNAs), mRNAs (DEmRNAs), and miRNAs (DEmiRNAs). Databases, miRTarBase and DIANA-LncBas, were applied to identify RNA interactions. The enrichment of pathways for DEmRNAs was done by Enrich tool. Cytoscape and STRING were utilized for the development of a protein-protein interaction network of DEmRNAs and the identification of the top five hub genes. Eventually, based on DElncRNA-miRNA-DEmRNA connections and co-expressions, the lncRNA-associated ceRNA axes were constructed. Results of the present study showed that 39 DEmRNAs (e.g., CDK4, CDK6, CCNA2, CCND2, and HMGA2) are involved in the HB ceRNA network. Furthermore, 27 DElncRNAs (e.g., CRNDE, GAS5, LINC00205, and ZFAS1) were identified as regulating the mentioned mRNAs through sponging eight DEmiRNAs (e.g., hsa-miR-195-5p, hsa-miR-29c-3p, hsa-miR-22-3p, hsa-let-7c-5p, hsa-let-7g-5p). Analysis of pathway enrichment demonstrated the enrichment of DEmRNAs in "Pathways in cancer", "MicroRNAs in cancer", "Hippo signaling pathway", "Human papillomavirus infection", and "Cellular senescence". This study identified the ceRNAs networks important for the molecular mechanism of HB development.

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