DUOX2 (Dual Oxidase 2)

Cell counting kit-8 (CCK-8) assay, 5-Ethynyl-2'-deoxyuridine (EdU) assay, colony formation assay and Annexin V-FITC/PI assay were performed to detect the anti-cancer effects of HQD and EGFR-TKIs (1st generation EGFR-TKI gefitinib or 3rd generation EGFR-TKI Osimertinib) in different NSCLC cell lines. Moreover, the drug safety, anti-cancer effect and potential mechanism of the therapy of HQD and EGFR-TKIs were confirmed in vivo. HQD enhances the anti-cancer effect of EGFR-TKIs in NSCLC through ROS-mediated CSC makers inhibition by suppressing stat3/GPX4 axis to induce redox ratio, providing a novel strategy for the treatment of NSCLC patients.

It also highlighted the distinct immune infiltration features between the two diseases. These findings provide novel perspectives on the pathogenesis of IBD and CCA, thereby offering a basis for early screening of CCA in individuals with IBD.

Collectively, our findings reveal a novel TCN1/STAT4/DUOX2 regulatory axis that exacerbates PDAC progression by remodeling redox homeostasis. This signaling cascade may serve as a prognostic biomarker and a potential therapeutic target for ROS-directed precision therapy in PDAC.

Thus, at gut and lung barriers an expansion of neutrophil oxidases occurs that highlights proinflammatory and antimicrobial DUOX2 activity, while NOX1 function seems intricate with multiple inputs. Evaluation of these de novo expressed oxidases in other neutrophil-driven diseases will further uncover their contribution to host protection and pathogenesis.

HADHB overexpression is linked to 5FU resistance in CRC, indicating it as a potential therapeutic target, likely via the HADHB-DUOX2-ROS pathway.

These data reveal a novel type of ROS-controlled DNA damage response and demonstrate the fine-tuning of the cellular response to stress. The effects on genomic stability and carcinogenesis are discussed here.

Our data revealed that RP11-109D20.2 may have a considerable role in CRC progression. However, further functional analyses are essential to evaluate the probable role of RP11-109D20.2 as a potential diagnostic marker and its potential role in the dysregulation of cyclic nucleotide phosphodiesterase genes in CRC.

Our findings suggested BRAF V600E and TERT promoter co-mutations in thyroid cancer contributed to disease progression and poor prognosis via modulating specific molecular pathways. The expression of genes related to thyroid hormone synthesis in co-mutated PTC was significantly downregulated, which may cause iodine therapy resistance by down-regulating iodide transporters (SLC5A5, SLC26A4 and LRP2) and biosynthesis (TPO, DUOX2 and DUOXA2).

Our analysis of PTC among Indians revealed novel genetic alterations and molecular subtypes. We identified a germline mutation in the DUOX2 gene, associated with congenital hypothyroidism, as a potential risk factor of PTC. Additionally, we characterized distinct molecular subtypes, BRAF-RAS driven and iBR driven, and their clinical implications. These findings provide valuable insights into the genetic landscape of thyroid cancer in Indian patients and offer potential avenues for targeted therapies.

Elevated DUOX2 signalling contributes to epithelial barrier dysfunction, microbiome alterations and subclinical inflammation. Butyrate and HDAC inhibitors reversed these effects, indicating that DUOX2 may be a therapeutic target in IBD.

IL-17A-stimulated FAP organoids show increased DUOX2/DUOXA2 expression, Duox2 protein, and ROS production, leading to DNA damage, suggesting a mechanism by which these immune cells promote tumorigenesis. These findings suggest IL-17A(+)NKp44(-)ILC3s may contribute to a local environment that makes the epithelium more submissive for oncogenic transformation in FAP.

The decreased lactylation level of CA3 protein at the K36 residues, induced by SQLE, results in the loss of the anti-cancer effect of CA3. Together, this study has demonstrated that CA3 is a novel tumor suppressor in HCC, and delactylation of CA3 represents a newly identified mechanism by which HCC cells evade growth suppressors.