BMC medical genomics · 2026
The miR-4512/PDZK1IP1 axis in hepatocellular carcinoma: clinical significance, diagnostic value, and functional validation.
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Chen Xiang, Zhou Gui, Cen Lihang, Qin Shuang, Dai Meiyu
Аннотация
BACKGROUND: PDZK1IP1 is implicated in various cancers, but its role in hepatocellular carcinoma (HCC) remains unclear.
AIM: To investigate the expression, clinical significance, and biological function of the miR-4512/PDZK1IP1 axis in HCC.
METHODS: 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.
RESULTS: 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.
CONCLUSION: 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.
AIM: To investigate the expression, clinical significance, and biological function of the miR-4512/PDZK1IP1 axis in HCC.
METHODS: 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.
RESULTS: 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.
CONCLUSION: 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.