DDIT4 (DNA Damage Inducible Transcript 4)

Regulated in development and DNA damage response-1 (REDD1/DDIT4) is induced in response to environmental stress to restrain the mechanistic target of rapamycin complex 1 (mTORC1) signaling as an adaptive strategy to restore cellular homeostasis...Interestingly, RNA sequencing analysis reveals that the loss of the transcriptional regulator EVI-1/MECOM in cells deficient in REDD1/DDIT4 amplifies the ER stress-induced upregulation of TRAILR2/DR5, leading to enhanced apoptosis. In summary, our findings underscore the crucial role of REDD1/DDIT4 in regulating TRAILR2/DR5-induced caspase-8 activation and apoptosis under chronic ER stress, by inhibiting mTORC1 activity and promoting EVI-1/MECOM-mediated suppression of TRAILR2/DR5 gene expression.

Myeloid cells exhibited expression of immunomodulatory genes (RUNX3, DDIT4, IL4I1), and malignant T-cells expressed exhaustion-associated markers (CXCL13, SOCS3, F2R, ETV1), as opposed to AD and healthy control samples. Thus, our results provide a novel insight into the immune-stroma crosstalk in the tissue microenvironment of early-stage MF vs. AD skin lesions.

Similarly, CHOP and DDIT4 can enhance ER stress and proteotoxicity, thereby favouring paraptosis. This review is unique in exploring the dynamic interplay between autophagy and paraptosis in cancer cells, highlighting promising therapeutic targets for chemotherapy-resistant cancers.

Given LCD e-waste growth, improper disposal releases LCMs, risking ecosystem bioaccumulation. These findings underscore the need for stricter regulation of LCMs throughout their lifecycle-from production to waste management-to mitigate ecological and health risks, with β-alanylleucine serving as a potential monitoring tool for environmental contamination.

Our results nominate DDIT4 as a promising therapeutic target for HCC intervention. Further preclinical and clinical investigations are warranted to validate DDIT4's translational potential and explore targeted strategies to stabilize its tumor-suppressive functions.

Erastin (ER), a small-molecule compound, induces ferroptosis through ROS accumulation...Our findings highlight ASNS, CHAC1, PCK2, DDIT4, and ATF3/4 as potential biomarkers for ferroptosis in CRC. Monitoring the expression of these genes may help identify patients who are responsive to ferroptosis inducers and facilitate the development of personalized treatment strategies.

In addition, multi-center datasets and immunohistochemistry revealed a significant up-regulation of DDIT4, FURIN, PTTG1 and RIPK2 at transcriptional and protein expression levels in LUAD tissues compared to normal tissues. PTDGs are potential biological markers for prognostic risk stratification of patients with LUAD.

Importantly, multiomics analyses reveal a unique mechanism of action: APT NPs induce the upregulation of the stress-responsive gene DNA damage-inducible transcript 4 (DDIT4), which inhibits the mammalian target of the rapamycin complex 1 (mTORC1) signaling pathway...In vivo, the MCF-7 tumor-bearing mouse model confirms potent antitumor efficacy without significant side effects. This work not only introduces a hypoxia-insensitive PDT agent but also provides novel insights into the mechanistic interaction between transcriptional and metabolic regulation in PDT, highlighting the potential of AIE-active materials for cancer therapy.

This integrative molecular and phenotypic profiling of blood-derived components identified potentially distinct molecular signatures, such as overexpression of IL12, ANGPT1 downregulation and HIF1A downregulation, in the literature described as linked to the patient's beneficial prognosis. These findings suggest that advanced liquid biopsy techniques may provide complementary insights into prognostic biomarkers and therapeutic targets in HGSOC.

DDIT4 promotes CRC progression and is regulated by miR-200b-3p. Targeting the miR-200b-3p/DDIT4 axis may represent a novel therapeutic approach for CRC treatment.

These findings suggest that baicalein may represent a promising, non-toxic therapeutic option for endometrial cancer, particularly when used in combination with metformin. Further investigation is warranted to assess the clinical relevance of this strategy.

To mimic ChaC1 overexpression by inducing endogenous ChaC1 high expression, a complementary ChaC1-induction-based screening was performed and revealed proteasome inhibitors (e.g., bortezomib, ixazomib, delanzomib) as potent inducers of endogenous ChaC1 via ATF4-dependent transcriptional activation. This functional convergence demonstrates that ChaC1 activation, either achieved through genetic manipulation or pharmacological induction, creates a synthetic lethal context for AUR in HCC cells. Together, our study establishes a ChaC1-based pharmacological discovery platform that identifies proteasome inhibitor and auranofin combination as a mechanistically rational anti-HCC strategy, providing both methodological innovation in drug repurposing screening and immediate translational potential for HCC treatment.