USP32 facilitates tumor development and is correlated with poor clinical outcomes in hepatocellular carcinoma patients and is modulated by the E2F7/miR-218-5p axis

Transcription factor E2F7 exerts suppressive transcription effects and was validated as highly expressed in hepatocellular carcinoma (HCC) in our previous study. Based on the correlation between E2F7 and the dismal clinicopathological features in patients, we investigated the downstream regulators controlled by E2F7 in HCC progression and identified a potential E2F7/miR-218-5p axis facilitating HCC cell growth by stabilizing USP32, one of the important ubiquitin-specific peptidases. The expression profiles of miR-218-5p and USP32 were detected in HCC cell lines and patients’ specimens, combined with the analysis of the public databases. The clinicopathological features of 95 HCC patients were analyzed. Cellular functional experiments through the expression regulation of these genes were conducted in vitro . The chromatin immunoprecipitation and the Dual-luciferase reporter assays were carried out to demonstrate the interaction between the candidate genes. USP32 was aberrantly overexpressed in HCC, and its high expression was positively associated with poor clinical outcomes and served as an independent risk factor. USP32 depletion impaired HCC cell growth and miR-218-5p targeted USP32 mRNA, thereby acting as a suppressive upstream regulator in HCC. E2F7 directly binds to the promoter region of miR-218-5p and suppressively modulates the transcription activity. Modulation of the E2F7/miR-218-5p axis significantly impacts USP32 transcription and HCC cell growth. USP32 is a pivotal ubiquitin peptidase highly expressed in HCC and facilitates tumor development. The E2F7/miR-218-5p axis functions as an upstream regulatory mechanism that modulates USP32 expression through transcriptional suppression. These genes provide the possibility for innovative targets against HCC.