P4HA2 promotes glioma cell proliferation by interacting with Hsp27 to activate the EGFR/ERK signaling pathway

Gliomas have a poor prognosis and limited therapeutic options, so there is an urgent need to find new therapeutic targets. P4HA2 promotes tumor progression by enhancing cell proliferation and extracellular matrix remodeling, and its high expression has been associated with a poor prognosis in gliomas. In this study, we investigated how P4HA2 interacts with Hsp27 to activate the EGFR/ERK pathway, thus suggesting P4HA2 as a potential therapeutic target.

A total of 238 glioma tissue samples and 25 normal brain tissues were collected for analysis. Protein expression levels were assessed by immunohistochemistry on tissue microarrays (TMAs). Glioma cell lines were transfected with either siRNA or lentiviral vectors to achieve P4HA2 knockdown. Protein interactions and signaling pathway alterations were examined using Western blotting, quantitative PCR, co-immunoprecipitation, and GST pull-down assays. In vivo tumorigenicity was evaluated through orthotopic intracranial xenograft models in nude mice. Bioinformatic analyses were conducted using publicly available datasets from The Cancer Genome Atlas (TCGA). All statistical analyses were performed using R software and GraphPad Prism.

P4HA2 is overexpressed in glioma tissues and its expression is positively correlated with glioma grade and poor prognosis. P4HA2 overexpression was an independent predictor of poor survival in GBM patients. Knockdown of P4HA2 in glioma cells reduced proliferation and tumor growth, while its regulation of the EGFR/ERK signaling pathway was evidenced by decreased EGFR phosphorylation and downstream signaling. P4HA2 interacted with Hsp27, promoting EGFR phosphorylation and enhancing the EGFR/ERK pathway, further driving tumor progression.

This study highlights the oncogenic role of P4HA2 in gliomas and its potential as a therapeutic target. P4HA2 promotes glioma cell proliferation by activating the EGFR/ERK pathway through its interaction with Hsp27. These findings establish P4HA2 as a promising prognostic marker and therapeutic target, offering new directions for individualized glioma treatment.