Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy with limited prognostic markers and therapeutic options. This study presents a systems-level analysis of microRNA-centered regulatory alterations in ACC, focusing on miR‑466. Comparative network reconstruction revealed substantial topological differences between tumor and normal states, including increased connectivity, altered centrality distributions, and emergence of tumor-specific hubs. miR‑466 showed the highest normalized betweenness centrality in the tumor network but limited influence in normal tissue, suggesting a malignancy-associated regulatory role. Although median expression of miR‑466 was similar between tumors and normal tissues, tumors exhibited higher variability and a stage-dependent decline, with the most marked reduction between stages II and III. Correlation analysis identified strong inverse associations between miR‑466 and multiple oncogenic or mitosis-related transcripts, including CHEK1, MELK, CDC25A, and KIF11. Up to 20% of genes upregulated in ACC showed significant negative correlation with miR‑466, indicating broad post-transcriptional influence. Functional enrichment and PPI network analysis consistently highlighted pathways involved in cell cycle progression, mitotic checkpoints, and chromosomal stability. Prognostically, higher miR‑466 expression was associated with improved overall survival (HR ≈ 0.24) under optimized stratification, with time-dependent AUC values exceeding 0.7 across most follow-up periods. Finally, exploratory drug–gene interaction mapping identified several actionable targets of miR‑466, including those linked to approved or investigational anticancer compounds. These findings position miR‑466 as a central node in ACC-specific regulatory networks, with potential relevance as a biomarker and therapeutic modulator. Further experimental validation is warranted.
Javad Omidi (Thu,) studied this question.