PRMT3 (Protein Arginine Methyltransferase)

However, challenges persist regarding tissue specificity and off-target toxicity, necessitating further refinement. Collectively, these results provide a new molecular basis for therapeutic approaches targeting PRMT3.

Through virtual screening and functional validation, we identified licochalcone A (LCA) as a potent inhibitor of STIP1-driven ESCC proliferation in vitro and in vivo. In summary, these findings delineate a pro-tumorigenic signaling pathway whereby heat-induced STIP1 upregulation promotes ESCC glycolysis and growth via moonlighting functions that coordinate AHCY activity and LDHA methylation.

Of particular translational importance, high-throughput FDA-approved drugs library screening identifies acipimox as a potent PRMT3 inhibitor and chemoradiotherapy sensitizer. This study offers a tangible prospect for improving therapeutic outcomes in rectal cancer patients in a clinically relevant setting.

Interestingly, combined pharmacological inhibition of PRMT3 and IDO1 effectively disrupted the TFAP2A-IDO1-Kyn axis, overcoming radioresistance, activating anti-tumor immunity, and ultimately eradicating tumors. In conclusion, these findings delineate PRMT3-mediated Kyn metabolism as a mechanism of radioresistance and immune evasion in NSCLC, offering valuable insights for potential interventions for treating lung cancer patients.

Daporinad, dinaciclib, and sepantronium bromide were predicted as potential drugs for the majority of cancer types. Potential biomarkers had been identified that may predict responses to immunotherapy and improve survival outcomes for cancer patients. This study provided a detailed overview of the functional roles, genetic and epigenetic alterations, and prognostic significance of PRMTs in pan-cancer.

miR-194-5p inhibition or PRMT3 overexpression stimulated the malignant behaviors of HCC cells underexpressing circERBB3. In conclusion, circERBB3 targeted miR-194-5p to promote PRMT3 expression, thereby promoting HCC cell malignancy.

We developed a PRMTs-related prognostic model for assessing prognosis and immunotherapy responses in LUAD. This model was vital for developing more personalized and effective treatment plans for LUAD patients.

Among them, only GSK3368715 advanced to clinical trials but was discontinued in phase I due to inadequate efficacy and thrombosis toxicity. Notably, as anticipated, CM112 could target PRMT1's nonenzymatic function by downregulating the stability of the orphan receptor TR3, an effect not observed with the PRMT1 inhibitor MS023, that is in consistence with the previous findings. Taken together, CM112 represents a valuable tool for elucidating the unknown, methyltransferase-independent roles of PRMT1 in disease progression and pave the way for developing more potent and drug like PRMT1 degraders in future.

Anti-PD-L1 treatment reversed PRMT3-induced tumor growth and restored CD8+ T cell infiltration. Our research links PRMT3-mediated metabolic reprogramming and immune evasion, revealing that the PRMT3-PDHK1-lactate-PD-L1 axis may be a potential target for improving the efficacy of immunotherapy in HCC.

Such as hepatocellular carcinoma, colorectal cancer, ovarian cancer, and endometrial cancer. These findings offer new strategies and directions for cancer treatment, especially in enhancing the effectiveness of conventional treatment methods.

Lastly, blocking PRMT3 functions synergize with PD-1 blockade in HCC mouse models. Our study thus identifies PRMT3 as a potential biomarker and therapeutic target to overcome immunotherapy resistance in HCC.

Significantly, the combination of 11 and glycolysis inhibitor 2-DG has a notable synergistic antiproliferative effect by further reducing ATP production and inducing intrinsic apoptosis, thus further highlighting the potential therapeutic value of targeted PRMT3 degradation. These data clearly demonstrated that degrader 11 is a powerful chemical tool for investigating PRMT3 protein functions.