NR4A1 (Nuclear Receptor Subfamily 4 Group A Member 1)

Collectively, these findings identify ALDH2 as a key tumor suppressor in HNSC, including OSCC, and highlight the therapeutic potential of activating ALDH2, NR4A1, and TGM2. Moreover, stabilization of the ALDH2-ALDH6A1 complex may offer a viable strategy for disease prevention and treatment, even in the context of frequent ALDH2 mutations.

To investigate oxaliplatin (OXA)‑induced senescence in GC cells, cellular senescence was assessed by senescence‑associated β‑galactosidase (SA‑β‑Gal) staining, western blotting, immunofluorescence, and reverse transcription‑quantitative polymerase chain reaction for the senescence‑associated secretory phenotype (SASP) factors...The present study identified NR4A1 as a key regulated gene in chemotherapy‑induced senescence in GC and verified that the NR4A1/AKT‑metabolism axis is vital for the pivotal mechanism of TIS. These findings may provide a novel therapeutic strategy to optimize chemotherapy and develop 'one‑two punch' approaches targeting senescent tumor cells.

These findings suggest that DEP may promote endometrial carcinogenesis by triggering oxidative stress-mediated signaling crosstalk and accelerating cell cycle progression. This study establishes a multi-layered methodological framework-from computational screening and machine learning to experimental validation-offering novel mechanistic insights into the carcinogenic potential of environmental endocrine disruptors such as DEP.

This study provides new insights into the molecular mechanisms underlying the progression of GBM, emphasizing the role of SERPINE1 and its interaction with NR4A1 in promoting EMT and tumor invasion. Inhibiting the expression of SERPINE1 in GBM cells can prevent cell invasion, providing a potential strategy for the treatment of GBM.

Mechanistically, IL-6 drives formation of an immunosuppressive TIME by promoting protumour macrophage polarisation. This, in turn, suppress cytotoxic T cell infiltration, promoting Treg expansion, and impairing NK cell function, indicating that the targeting of IL-6 represents a promising strategy to overcome resistance to chemoimmunotherapy.

In summary, the current study elucidated that low KMO expression in HCC affects mitochondrial mass and function by reducing the level of the Try metabolite 3‑HAA, downregulating the expression of NR4A1 and promoting its mitochondrial translocation, which in turn may promote the progression of HCC. These findings provide new insights into the treatment of HCC, potentially targeting the mitochondria and the Try‑Kyn pathway..

This external validation confirms the seven-gene signature as a potential biomarker for predicting ICI efficacy in advanced sarcomas. Prospective studies are needed to determine the prognostic versus predictive value of SIGNIOS, refine its use across sarcoma subtypes, and explore its applicability in other tumor types.

Collectively, EC@HNA dismantled the stemness-immunity axis sustaining ENZR and restored robust anti-tumor immunity with minimal systemic toxicity. Overall, the CD44-targeted EC@HNA nanoplatform disrupted stemness programs and restored tumor-immune surveillance, representing a promising strategy to reverse ENZR and potentiate immunotherapy in clinical ENZR PCa patients.

WB was used to assess activation of the c-Jun N-terminal kinase (JNK)/p38 mitogen-activated protein kinase (MAPK) pathway, and pathway dependence was examined using the ROS scavenger N-Acetylcysteine (NAC) and the JNK inhibitor SP600125. It exerts anti-tumor effects by inducing oxidative stress and activating the JNK/p38 MAPK pathway in a ROS-dependent manner. These findings suggest that CSRNP1 may serve as a potential therapeutic target in the management of HCC.

A rescue experiment revealed that NR4A1 knockdown partially reversed the Antagomir-150-induced up-regulation of P4 synthesis and apoptosis. Overall, this study demonstrates that miR-150 contributes to P4 synthesis and apoptosis in goat luteal cells by targeting NR4A1.

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.

How the oncogenic and tumor-suppressor roles of orphan nuclear receptor 4A1 (NR4A1) are balanced remains unclear. In this issue of Molecular Cell, Cai et al.1 report that a pyrimidine metabolite-UMP-acts as an endogenous regulator of NR4A1 by directly binding to abrogate its suppressive effect on gastric cancer development.