NR4A2 (Nuclear Receptor Subfamily 4 Group A Member 2)

Our study establishes a novel multi-gene diagnostic signature for oxaliplatin resistance through integrative bioinformatics and machine learning approaches. The comprehensive molecular characterization and identification of potential therapeutic candidates provide new insights into resistance mechanisms and clinical management strategies for oxaliplatin-resistant colorectal cancer.

Further treatment with CXCL5 ligand significantly induced neuritogenesis, while the neurite outgrowth was abrogated when cotreated with CXCR2 (receptor for CXCL5) inhibitor SCH527123...NR4A2 knockdown in UMSCC1 cells impaired tumor formation in vivo, and the xenograft tissues exhibited significant downregulation of CXCL5, providing direct in vivo evidence for the NR4A2-CXCL5 axis in tumor progression. NR4A2 is a key driver of CXCL5-mediated PNI and the NR4A2/CXCL5/CXCR2 signaling axis is a potential therapeutic target in HNSCC and PDAC.

Crucially, the anti-tumor efficacy of L. johnsonii was CD8+ T cell-dependent, as depletion abolished its activity. This work unveils a mechanism by which L. johnsonii and its metabolite NA enrich intratumoral IFN-γ+PD-1+CD8+ T cells, thereby reshaping the immune microenvironment to potentiate immunotherapy efficacy and suppress HCC recurrence.

We have also identified gene silencing, reduced gene expression of key transcription factors that regulate mitochondrial biogenesis, as well as increased long non-coding RNA as potential drivers of this unique metabolic phenotype. These results highlight the potential benefit of targeting metabolism in sepsis to promote immune homeostasis and recovery.

Plasma proteomics revealed shared mediators including interleukin-6 and EN-RAGE across anatomical sites and ages. Together, our findings delineate anatomical-specific and age-specific immune programs in sepsis, highlighting candidate targets for precision immunotherapy.

Transcriptome cluster comparative analysis placed its expression profile close to pancreas neuroendocrine tumors. This case suggests NR4A2 as a functionally substitute for NR4A3 in tumorigenesis and a neuroendocrine lineage differentiation for a subset of EMC.

By focusing on RNA instead of DNA, we expand our understanding of the carcinogenic mechanisms of HPVint, in part addressing the conflicting findings of whether HPVint is associated with aggressive phenotypes and worse clinical consequences and provide potential biomarkers to advance precision oncology in HPV-associated HNSCC. Newly identified genes with recurrent integration events may serve as candidates for targeted therapy.

P1/2, N=35, Enrolling by invitation, State University of New York at Buffalo | Trial completion date: May 2026 --> Nov 2026 | Trial primary completion date: Feb 2026 --> Jun 2026

While SH-SY5Y cells exhibited dopaminergic characteristics following the blended differentiation protocol, the transient expression of key neuronal markers and the need for continuous external stimuli raised concerns about the stability and functional maturity of these differentiated cells as an in vitro PD model. These findings suggest that SH-SY5Y cells might not fully capture the properties of mature neurons.

Moreover, both promoter and ChIP analysis indicated that NR4A1 and NR4A2 acted as ligand-dependent cofactors of Sp1/4-mediated expression of CD71 in TNBC cells. Thus, CD71, a key biomarker of ferroptosis is an NR4A1/2/Sp regulated gene that can be directly targeted by DIM-3,5 inverse NR4A1/2 agonists to induce ferroptosis in TNBC cells.

Treatment of AML cells with NR4A ligands significantly reduced M.tb growth while treatment with an NR4A antagonist significantly increased it. In conclusion, we identify the expression, location, and apoptotic activity of NR4A NRs in human macrophages and their potential as new TB HDT therapeutic targets.

Mice lacking Nr4a2 in Car3 ensembles during the embryonic stage or in adulthood display hyperactivity and reduced anxiety-like behaviors. Therefore, our results demonstrate that Nr4a2 is a key factor in regulating the development and functional maintenance of the forebrain Car3 neurons.