# P3H4 Enhances the Proliferation, Invasion, and Glycolysis of Hepatocellular Carcinoma Cells

**Authors:** Lili Yan, Yandan Fan, Ji Lv, Meimei Xu, Hongyu Jia, Shanshan Li, Zhihui Tan, Chunyan Lin

PMC · DOI: 10.1155/ijog/2532296 · International Journal of Genomics · 2025-11-09

## TL;DR

This study shows that P3H4 promotes liver cancer growth and spread by enhancing cell proliferation, invasion, and glycolysis through the PI3K/AKT pathway.

## Contribution

The study identifies P3H4 as a novel driver of hepatocellular carcinoma progression via the PI3K/AKT pathway.

## Key findings

- P3H4 expression is elevated in liver tumors and correlates with poor patient survival.
- Knocking down P3H4 inhibits HCC cell proliferation, invasion, and glycolysis.
- P3H4 knockdown reduces tumor growth and Ki-67 expression in mouse models.

## Abstract

The study is aimed at investigating the functions of P3H4 in liver cancer.

The TCGA and CPTAC liver cancer databases were utilized to analyze the expression levels of P3H4 and its associated survival rates between tumor and normal tissues. A cohort of 60 HCC patients was selected based on criteria for P3H4 expression and survival analysis. qRT‐PCR and western blotting techniques were employed to assess P3H4 expression in cell lines. The CCK8 assay was conducted to compare cell viability between normal and P3H4‐knockdown HCC cell lines. A glycolysis detection kit was used to measure glucose, lactate, and ATP levels following P3H4 knockdown. A nude mouse tumorigenicity assay was performed by injecting Huh7 cells treated with sh‐NC or sh‐P3H4; tumor volume and weight were recorded, and tumor tissues were collected for IHC analysis.

P3H4 expression was found to be elevated in liver tumors compared to normal tissues, as indicated by both database analyses and patient data. High expression of P3H4 correlated with poorer survival and prognosis in patients. Knocking down P3H4 significantly inhibited HCC proliferation, invasion, glycolysis, and PI3K/AKT phosphorylation in HCC cell lines. Results from the nude mouse tumorigenicity assay demonstrated that the average tumor volume, tumor weight, and the percentage of Ki‐67 positive cells were significantly reduced in the sh‐P3H4 group compared to the sh‐NC group.

P3H4 promotes HCC proliferation, invasion, and glycolysis through the PI3K/AKT pathway, providing new insights into the diagnosis and treatment of HCC.

## Linked entities

- **Genes:** P3H4 (prolyl 3-hydroxylase family member 4 (inactive)) [NCBI Gene 10609], PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) [NCBI Gene 5290], AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207]
- **Diseases:** hepatocellular carcinoma (MONDO:0007256), liver cancer (MONDO:0002691)
- **Species:** Homo sapiens (taxon 9606)

## Full-text entities

- **Genes:** AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, PIK3CB (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta) [NCBI Gene 5291] {aka P110BETA, PI3K, PI3KBETA, PIK3C1}, P3H4 (prolyl 3-hydroxylase family member 4 (inactive)) [NCBI Gene 10609] {aka LEPREL4, NO55, NOL55, SC65}
- **Diseases:** tumorigenicity (MESH:D002471), tumor (MESH:D009369), liver tumors (MESH:D008113), HCC (MESH:D006528)
- **Chemicals:** ATP (MESH:D000255), glucose (MESH:D005947), lactate (MESH:D019344)
- **Species:** Homo sapiens (human, species) [taxon 9606], Mus musculus (house mouse, species) [taxon 10090]
- **Cell lines:** Huh7 — Homo sapiens (Human), Adult hepatocellular carcinoma, Cancer cell line (CVCL_0336)

## Full text

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## Figures

22 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12597767/full.md

## References

28 references — full list in the complete paper: https://tomesphere.com/paper/PMC12597767/full.md

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Source: https://tomesphere.com/paper/PMC12597767