PTGES (Prostaglandin E Synthase)

This study confirmed that PGE2 promotes immune evasion of NSCLC by upregulating PD-L1, and the mechanism involves the activation of the PI3K/AKT/mTOR pathway. This research provides a novel theoretical basis for immunotherapy of NSCLC and emphasizes the clinical value of PTGES/PGE2 as a potential target.

A TRGs-based prognostic model effectively predicts survival in EC and reveals associations with somatic mutations, immune infiltration, and drug sensitivity. Functional validation of PTGES3 further supports its potential as a therapeutic target.

Mechanistically, we show PTGES3 binds directly to AR, regulates AR protein stability and is necessary for AR function in the nucleus at AR target genes. PTGES3 represents a potential therapeutic target for overcoming known mechanisms of resistance to existing AR-directed therapies in PCa.

ZBTB7A was identified as a key regulator of PTGES3, while interactions among LGALS9, P4HB, and CD44 significantly impacted signaling pathways influencing the tumor microenvironment's immune status. Our findings highlight the potential of LS score-based molecular subtyping to improve treatment strategies for lung adenocarcinoma and emphasize PTGES3's role in new therapeutic development.

Furthermore, overexpressing PTGES upon the TFAP2C silence restored the great inhibition effect conferred by TFAP2C silence in PC-9/GR cells on cell viability and cell response to gefitinib resistance. This study confirmed that TFAP2C can transcriptionally activate PTGES through the NOTCH3 signaling pathway to enhance the response of LUAD cells to gefitinib resistance, proffering a new approach for the treatment of gefitinib resistance in LUAD cells.

Mechanistically, we show PTGES3 binds directly to AR, forms a protein complex with AR in the nucleus, regulates AR protein stability in vitro and in vivo and modulates AR function in the nucleus at AR target genes. PTGES3 represents a novel therapeutic target for overcoming known mechanisms of resistance to existing AR-directed therapies in PCa.

CTSH overexpression or PTGES3 knockdown induced necroptosis and improved anti-PD1 therapy efficiency in syngeneic cancer mouse models. These findings indicate necroptosis genes as potential therapeutic targets in cancer treatments.

Our study revealed that the AEP/PGE2 feedback loop modulates tumour-induced neuronal senescence upon radio-/chemotherapy and highlight the therapeutic value to improve tumour therapy.

Genes for PGE2 synthase enzymes, PGE2 receptors, HIF1α and VEGFA were expressed in FOSCC cells in vitro. SCCF2 cells responded to exogenous PGE2 and EP4 antagonism, suggesting that EP4 activity in FOSCC deserves more study.

Elevated expression of PTGES3 was linked to immunosuppressive cascades, diminished responsiveness to immunotherapy, and inferior overall survival outcomes. Molecular docking analysis indicated that etoposide, methotrexate, and doxorubicin could effectively bind to PTGES3. In vitro experiments confirmed that PTGES3 knockdown significantly impaired the proliferation, invasion, and migration of HCC cells. This study highlights the pivotal role of lipid metabolism in HCC progression and identifies PTGES3 as a potential prognostic biomarker and therapeutic target. These findings offer new insights into the development of targeted therapies for HCC, particularly in patients with high PTGES3 expression.

Our findings revealed that the highly selective PTGES3 proteolysis is a potential therapeutic strategy for HCC, and PTGES3 degraders PTGES3-PROTACs can be developed as safe and effective drugs for HCC treatment.

Targeting PGE2 signalling in PTGES-overexpressing cells by a PTGES inhibitor reduced α-SMA expression. In conclusion, the results of this study demonstrate that PTGES increases the expression of myofibroblast marker via HIF-1α-dependent glycolysis and contributes to myofibroblast differentiation.