Unraveling the ceRNA Network: Insights into PI3K-AKT Pathway in Irradiated Mouse Thymus [miRNA]

Background: Excessive or inappropriate radiation exposure can cause serious damage to organisms. Radiation-induced thymus injury (RITI) is a serious complication associated with radiation and is mediated by RNAs. Methods: The thymus tissues of mice were analyzed using RNA-sequencing (RNA-seq) and their libraries 24 h after exposure to 6 Gy of X-ray radiation. The target mRNAs were functionally annotated and the target lncRNA-based miRNAs and miRNA-based mRNAs were predicted after irradiation to develop the lncRNA-miRNA-mRNA ceRNA axis. Results: The results revealed that after irradiation, 6214 mRNAs, 160 miRNAs, and 1999 lncRNAs were significantly upregulated while 2676 mRNAs, 165 miRNAs, and 941 lncRNAs were considerably downregulated. Angiogenesis and ameboidal-type cell migration for Biological Process; actin cytoskeleton and extracellular matrix (ECM) for Cellular Component; and actin binding and ECM structural component for Molecular Function represent the most prominent changes in GO analysis function. A total of 333 cellular function were significantly altered by PTEN, while 175 CFs were substantially changed by PDPK1. Pathways involved in cancer, ECM-receptor interaction, focal adhesion, axon guidance, PI3K-AKT signaling, and adrenal signaling in cardiomyocytes were identified via KEGG pathway analysis. For experimental confirmation, the crucial pathway PI3K-AKT was selected to have a role in thymus degeneration after radiation exposure. Conclusion: A lncRNA-miRNA-mRNA ceRNA axis of RITI was successfully developed in a mouse model after irradiation. The PI3K-AKT pathway contributes to preventing radiation-induced cell death in RITI, and the differentially expressed RNA in the initial stage of this injury may result in serious consequences. Overall design: Thymus lncRNA,mRNA and miRNA profiles of 5 weeks old control and 1d after radiation group mice were generated by deep sequencing, in triplicate, using Illumina GAIIx.