Unlocking the potential of LHPP: Inhibiting glioma growth and cell cycle via the MDM2/p53 pathway

The recurrence of glioma after treatment has remained an intractable problem for many years. Recently, numerous studies have explored the pivotal role of the mouse double minute 2 (MDM2)/p53 pathway in cancer treatment. Lysine phosphate phosphohistidine inorganic pyrophosphate phosphatase (LHPP), a newly discovered tumor suppressor, has been confirmed in numerous studies on tumors, but its role in glioma remains poorly understood. Expression matrices in The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) databases were analyzed using gene set enrichment analysis (GSEA), revealing significant alterations in the p53 pathway among glioma patients with high LHPP expression. The overexpression of LHPP in glioma cells resulted in a reduction in cell proliferation, migration, and invasive ability, as well as an increase in apoptosis and alterations to the cell cycle. The present study has identified a novel inhibitory mechanism of LHPP against glioma, both in vivo and in vitro. The results demonstrate that LHPP exerts anti-glioma effects via the MDM2/p53 pathway. These findings may offer a new perspective for the treatment of glioma in the clinic. [Display omitted] •This study identifies a new mechanism for LHPP anti-tumor effect.•We found that high expression of LHPP was significantly associated with the p53 signaling pathway by GSEA analysis of public databases.•Tumor suppressor p53 has a key role in glioma development•High expression of LHPP brought about an increase in p53 protein levels.•High expression of LHPP inhibited MDM2 expression and reduced ubiquitination of p53.•Inhibition of the p53 pathway resists the antitumor effects of LHPP.•LHPP exerts its anti-tumor effects in vivo through the p53 pathway.