Metabolic reprogramming in cancer cells, including the activity of enzymes like PHGDH, alters gene expression networks and is closely linked to tumor progression, offering new avenues for cancer therapy.

Recent research using UV crosslinking-based RNA interactome capture has revealed that PHGDH, a metabolic enzyme, acts as a crucial RNA-binding protein that stabilizes the mRNA of PRKCD, thereby promoting mitophagy in hepatocellular carcinoma (HCC) cells.

This stabilization of PRKCD mRNA by PHGDH enhances its protein levels, which contributes to the progression of HCC, highlighting a novel non-enzymatic role for PHGDH in cancer.

In vivo studies have shown that targeting PHGDH in mouse models significantly reduces tumor growth, suggesting its potential as a promising therapeutic target for HCC.

Beyond its enzymatic role in serine biosynthesis, PHGDH is upregulated in various cancers and influences tumor progression through its RNA-binding functions, affecting gene regulation and cell survival.

Hepatocellular carcinoma remains a leading cause of cancer-related death with increasing incidence, often diagnosed at advanced stages when treatment options are limited, emphasizing the urgent need for novel therapeutic strategies.

Decoy oligonucleotides designed to inhibit PHGDH’s RNA-binding activity have been effective in suppressing HCC progression by decreasing PRKCD expression and associated mitophagy.

The study indicates that the PHGDH-PRKCD axis correlates with poor prognosis in HCC patients and could serve as a valuable target for combination therapies.