RELA (RELA Proto-Oncogene)

Notably, SIRT1 overexpression attenuated the MMDD-induced DC maturation and CD8+ T cell activation, confirming the involvement of SIRT1/acetyl-p65 signaling. Collectively, MMDD exerts potent anti-NSCLC activity by facilitating DC maturation via the SIRT1/acetyl-p65 axis, highlighting its potential as an immunomodulatory therapeutic strategy for NSCLC.

Our findings indicate that Grg3 confers protective effects in a murine model of imiquimod-induced psoriasis-like dermatitis. The potential therapeutic properties of Grg3 potentially involve modulation of NLRP3 inflammasome activation, suppression of NF-κB signaling, and restoration of Th17/Treg cell homeostasis.

We successfully developed TIPE2-downregulated NKG2D-CAR-T cells that exhibited enhanced activation and cytotoxicity while limiting apoptosis and exhaustion against NKG2D ligand-expressing pancreatic tumors, highlighting TIPE2 as a promising intracellular immune checkpoint target for optimizing CAR-T cell therapy in solid tumors.

Furthermore, kaempferol treatment reduced phosphorylated Akt expression and NF-κB p65 activity. These findings indicate that kaempferol suppresses the migratory and invasive abilities of PaCa cells by downregulating MMP-1 through negative regulation of the Akt and NF-κB signaling cascades, while kaempferol holds promise as a treatment strategy for GEM-R PaCa.

For example, genetic association for a previously undescribed isoform of endothelial protein C receptor (PROCR) colocalized with genetic risk for deep vein thrombosis and coronary artery disease with opposing risk alleles. This study demonstrates the prevalence of inducible promoters upon inflammatory stimuli and shows that genetic risk for vascular disease may be in part governed through AS in ECs.

Notably, over 80% of genes upregulated in ZFTA-RELAfus tumors were downregulated following MERTK inhibition, indicating a strong dependency on this pathway for tumor maintenance. These findings define a signaling vulnerability in ZFTA-RELA-driven ependymomas and support the clinical development of MERTK-targeted therapies for patients with the high-risk EPN-E1 subtype.

Clinically approved drugs such as Dasatinib (targeting CSK) and Crizotinib (targeting MET) emerged as promising candidates due to favorable pharmacokinetics and known bioactivity. Host-directed therapeutics could offer alternative strategies to conventional antibiotic therapy, addressing challenges such as resistance and infection recurrence, providing a foundation for future experimental validation and development of host-targeted interventions for infection control.

Taken together, our results position itaconate upregulation as a previously unappreciated driver of ZFTA-RELA+ ependymomas. Our work has implications for future drug development to reduce pathogenic ZFTA-RELA expression for this brain tumour, and will advance our understanding of oncometabolites as a new class of therapeutic dependencies in cancers.

Remarkably, normalizing hematopoiesis with a single infusion of antibodies directed against cytokines enriched in the cerebrospinal fluid of mice bearing ZFTA-RELA ependymomas, choroid plexus carcinomas or group 3 medulloblastoma-all aggressive childhood brain tumors-disrupted this process and caused profound tumor regression. These findings demonstrate the existence of a skull bone marrow-tumor immunological interface and suggest that modulating the local supply of myeloid cells could represent a less toxic therapeutic strategy for aggressive childhood brain tumors.

Supratentorial ependymomas with ZFTA-RELA fusions represent a highly aggressive pediatric brain tumor subtype, yet the post-transcriptional mechanisms driving their malignancy remain unclear. This study fills a critical gap by systematically profiling miRNA expression in fusion-positive and fusion-negative supratentorial ependymomas, revealing a distinct fusion-associated miRNA signature. The identification of hsa-miR-138-5p upregulation and hsa-miR-135b-5p/hsa-miR-216a-3p downregulation, converging on key oncogenic nodes such as TERT, YAP1, RELA, and TP53, provides novel mechanistic insight into how fusion-driven miRNA dysregulation enhances epithelial-mesenchymal transition and stemness. The findings suggest that miRNA-fusion interactions play an important role in tumor aggressiveness and highlight hsa-miR-138-5p as a potential biomarker for disease progression. Clinically, the work advances understanding of fusion-driven ependymoma biology and lays the foundation for developing miRNA-based diagnostic and therapeutic strategies targeting molecular mechanisms of tumor progression.

High IER3 expression correlates with reduced response to immune checkpoint blockade (ICB) and distinct drug sensitivity profiles. Together, these findings confirm that IER3 is a dual critical mediator of CRC progression and immune escape, highlighting its potential as a therapeutic target and biomarker for personalized treatment strategies.

SB may regulate TRP-induced bone metabolism abnormalities in LNCaP cells through the IL-17 signaling pathway as well as five DEPs: p-ERK2, RELA, HSP90B1, GNAI1and GNAI3.