The miR-4512/PDZK1IP1 axis in hepatocellular carcinoma: clinical significance, diagnostic value, and functional validation

PDZK1IP1 is implicated in various cancers, but its role in hepatocellular carcinoma (HCC) remains unclear.

To investigate the expression, clinical significance, and biological function of the miR-4512/PDZK1IP1 axis in HCC.

Serum samples from 56 HCC patients, 57 cirrhosis patients, and 68 healthy controls were analyzed by qRT-PCR. Diagnostic and prognostic values were assessed by ROC curves and Kaplan-Meier/Cox regression analyses, respectively. The regulatory relationship was validated by dual-luciferase assay. Functional roles and downstream mechanisms were examined via cellular assays and Western blotting.

Serum miR-4512 was significantly downregulated while PDZK1IP1 was upregulated in HCC patients, showing a negative correlation. Both markers served as independent prognostic factors for overall survival and disease-free survival. A triple diagnostic combination (miR-4512 + PDZK1IP1 + AFP) achieved an outstanding AUC of 0.988. Dual-luciferase assay confirmed miR-4512 directly targeted the 3’UTR of PDZK1IP1. Functionally, miR-4512 overexpression or PDZK1IP1 silencing suppressed HCC cell proliferation, migration, and invasion. Mechanistically, Western blot revealed that miR-4512 suppressed the Akt/mTOR signaling pathway and glycolysis, which was robustly reversed by PDZK1IP1 overexpression.

The miR-4512/PDZK1IP1 axis regulates HCC progression via the Akt/mTOR and glycolysis pathways. Both molecules demonstrate significant potential as robust diagnostic and prognostic biomarkers for HCC.