P4HB (Prolyl 4-Hydroxylase Subunit Beta)

P4HB promoted migration, invasion, and EMT of bladder cancer cells by activating the Claudin-1/AMPK/TGF-β1-related pathway.

Mechanistically, P4HB promoted STAT3 phosphorylation in microglia, driving their pro-tumorigenic M2 phenotype. These findings establish P4HB as a regulator of glioma progression via IL-6/STAT3-mediated microglial polarization, highlighting its potential as a therapeutic target for GBM.

These findings highlight the pivotal role of ACTG1 in regulating EMT in BLCA through its splicing activity on P4HB, suggesting new therapeutic targets for intervention. This study underscores the critical importance of splicing regulation in cancer biology, offering novel insights for diagnostic and therapeutic strategies in BLCA.

Furthermore, we identified a novel interaction between P4HB and the lncRNA UCA1, which enhances glycolysis and malignant behavior in HCC cells. These findings suggest that P4HB is a promising biomarker for HCC diagnosis and a potential therapeutic target, particularly in the context of its interaction with UCA1.

P4HB inhibited the activation of the NF-kB pathway by promoting the expression of LGALS3BP, thus promoting the progression of MIA to IAC. This provides a new target for the clinical diagnosis and treatment of LUAD.

SOX4 and P4HB seem to have diagnostic and prognostic value in PAC. While there was a direct correlation between SOX4 and P4HB, an inverse relationship between SOX4 and ERG was detected.

We found higher levels of immune cell infiltration and better responses to immunotherapy and cisplatin chemotherapy in the high PMRI group than in the low PMRI group, which can also be used to predict immune efficacy in a variety of solid tumors other than BCa...We performed molecular docking prediction for each of the core proteins comprising PMRI and identified 16 small-molecule drugs with the highest affinity to the target proteins. Our PD-L1 multidimensional expression regulation model based on anti-PD-L1 immunotherapy-related genes can accurately assess the prognosis of patients with BCa and identify patient populations that will benefit from immunotherapy, providing a new tool for the clinical management of intermediate and advanced BCa.

The widespread expression of P4HB gene and its interaction with LGALS9 was also notable. Our findings point to a profound role of TAMs via LGALS9 and its interaction with P4HB that should be considered for further elucidation as target in the combinatory immunotherapies for PDAC.

These results demonstrate that circP4HB could promote LUAD progression, indicating circP4HB might be a potential therapeutic target of LUAD.

In this study, we found that P4HB might serve as a prognostic biomarker and predict radiotherapy resistance for PCa patients. Downregulation of P4HB expression could inhibit the cell proliferation of PCa cells.

In a pre-clinical model of different PC lines made in our laboratory, inhibition of PDIA1 using CCF642-34 was highly effective, with bortezomib (BTZ) resistant MM cells being 2X more sensitive compared to BTZ naïve cells... Here we demonstrate that the resistance to PI in patients with MM occurs, in part, due to the gain in the ER function, primarily via upregulation of PDIA1, an ER resident disulfide isomerase, critical for protein folding. The increased dependence of MM cells on ER function makes them highly vulnerable to PDIA1 disruption, particularly upon PI resistance acquisition. We have developed a next generation orally bioavailable PDIA1 inhibitor that demonstrated high therapeutic index in pre-clinical model systems.

It was suggested that FN1 could be an ideal target for prognosis and a potential therapeutic target in GBM.