miR-507 and miR-665 as Central MicroRNA Regulators in the ceRNA Network of Adrenocortical Carcinoma: A Systems Biology Approach

MicroRNAs (miRNAs) are key regulators of post-transcriptional gene expression and have been increasingly implicated in the pathogenesis of rare malignancies such as adrenocortical carcinoma (ACC). Here, a systems biology approach was employed to construct and analyze context-specific competing endogenous RNA (ceRNA) networks using transcriptomic profiles from 78 ACC tumors (TCGA) and normal adrenal tissues obtained from both GTEx 2025 and miRNATissueAtlas 2025 datasets, leveraging a novel integrative analytical framework specifically developed in this study. Comparative network topology revealed extensive regulatory rewiring in tumors, with miR-507 and miR-665 emerging as tumor-specific central miRNAs. While miR-507 was significantly upregulated and associated with favorable patient survival, miR-665 was downregulated and displayed radiation-sensitive expression dynamics. Target gene prediction and correlation analyses identified distinct sets of oncogenic and tumor-suppressive genes regulated by each miRNA. Functional enrichment and PPI network analysis indicated that miR-507 targets are strongly enriched in cell cycle, mitotic checkpoint, and chromosomal stability pathways, whereas miR-665 influences more context-dependent immune and signaling mechanisms. These findings support the prognostic and therapeutic potential of miR-507 in ACC and suggest a radiotherapy-modulated regulatory role for miR-665. Overall, this study demonstrates the power of multi-source transcriptomic integration for discovering functional miRNA hubs in rare endocrine cancers.