SOCS3 (Suppressor Of Cytokine Signaling 3)

For perturbation, the EZH2 inhibitor tazemetostat was evaluated in the CRPC-relevant C42 cell line with H3K27me3 readouts and transcriptomic profiling, with key changes validated by RT-qPCR...This multi-layer integrative analysis suggests that EZH2 is associated with proliferative malignant states and immunosuppressive microenvironment features in advanced PCa, including Treg-linked crosstalk. Transcriptomic profiling following EZH2 inhibition supports modulation of these programs by EZH2-targeted perturbation, while functional and causal mechanisms warrant further investigation.

Notably, the inhibitory effect of CL-E on STAT3 Tyr705 phosphorylation was reversed by MEK1/2 (U0126) or PKC inhibitors (bisindolylmaleimide II), indicating that CL-E modulates STAT3 signaling through an ERK-mediated mechanism. Collectively, these in vitro findings identify C. longa leaves as an underutilized botanical resource with the potential to regulate IL-6/STAT3 signaling, warranting in vivo evaluation to establish its efficacy, safety and pharmacokinetics, and to define potential therapeutic utility in IL-6/STAT3-driven conditions.

We propose that lidocaine can be repurposed as an immunomodulator for treating immune-mediated inflammatory diseases. However, future research should define optimal dosing strategies, validate its mechanisms of action in clinical trials, and explore its novel clinical applications as a complementary immunotherapy.

Functional assays demonstrated that DHA-treated cells exhibited increased secretion of TNF, IL1β, ROS, and PD-L1, accompanied by enhanced cytotoxic activity against hepatocellular carcinoma cells in a co-culture system. These findings reveal the molecular mechanisms underlying TAN polarization, and establish DHA as a potent immunomodulatory agent capable of reshaping TANs toward an anti-tumor phenotype.

It indicates that FosB plays a critical role in the pathogenesis of NASH, and its expression is associated with the prognosis of patients with HCC. Further experimental studies are required to investigate the potential targeting of FosB in NASH and NASH-induced HCC.

Importantly, the pharmacologic inhibition of glycolysis with 2-deoxy-d-glucose restored SOCS3 secretion in these AMs. Together, our findings demonstrate that lung tumor-associated AMs undergo a time-dependent metabolic shift toward glycolysis, resulting in impaired SOCS3 secretion-a phenotype that can be reversed by targeting glycolytic flux. These results highlight a potential therapeutic approach for modulating immune suppression in the tumor microenvironment.

Molecular docking further predicted that Glu63 of SOCS3 serves as a key residue for MLN4924 binding. Together, low-dose MLN4924 enhances SH-SY5Y cell viability and migration by targeting SOCS3 signaling, independent of JAK2/STAT3 signaling.

These findings elucidate the mechanisms underlying granuloma formation in sarcoidosis and demonstrate the differential transcriptomic features of PBMCs in patients with and without EPL. The upregulation of IFNG and IFNLR1 may be related to EPL development and could serve as potential therapeutic targets for sarcoidosis.

GPM6B promoted the transformation of glioma stem cells and inhibited growth of glioma by suppressing Integrin β1-mediated regulation of β-catenin, while reducing its own degradation through inhibition of the ubiquitinase SOCS3, thereby stabilizing its function in glioma. Collectively, these results identify GPM6B as a critical regulator of glioma stemness and a potential therapeutic target for glioma, providing new insights into glioma biology and offering a foundation for future translational research.

Collectively, this study identifies critical SOCS3 SNPs that may modulate protein function and contribute to MFD pathogenesis. These findings suggest that SOCS3 missense SNPs, particularly E98V, H126Y, and A223S, may serve as candidate biomarkers for cancer susceptibility and warrant further experimental validation.

Therefore, our study results suggest the significance of genotypic and haplotype analysis of SOCS3 gene polymorphisms and its impact on progression and risk prediction of breast cancer.

Additionally, this process involves the assistance and balance of the reader YBX1 and the eraser TET2. NSUN2 methylates SOCS3 mRNA to inhibit its stability and nuclear export, which consequently promotes macrophage polarization to M2.