DDX1 (DEAD-Box Helicase 1)

It further confirmed its pivotal role in CCA progression. Targeting the USP10-PRMT1-DDX1 axis may represent a significant therapeutic approach for CCA.

We have shown that 2p24.3 microduplications that include MYCN predispose to childhood embryonal tumours and should be routinely assessed when WT or neuroblastoma predisposition is suspected. We have also shown that there does not appear to be any increased incidence of childhood tumours when DDX1 alone is duplicated.

Rescue experiments demonstrated that re-expression of Sh2b1-T1, but not Sh2b1-T2, reversed the impairment of osteoblast differentiation triggered by Ddx17 knockdown. Taken together, these findings underscore the critical role of the Prmt1-Ddx17-Sh2b1 axis in regulating osteoblast differentiation and suggest this axis as a promising therapeutic target for osteoporosis.

Clinical bioinformatics analyses further reveal that elevated expression of USP45, RTCB, and DDX1 correlates with poor patient survival. Our findings establish the USP45-RTCB-DDX1 axis as a dual driver of oncogenesis and chemoresistance via specific RTCB/DDX1 post-translational stabilization, nominating USP45 inhibition as a therapeutic strategy to suppress cancer progression and overcome treatment resistance.

We present a robust high-throughput in vitro assay designed for small molecule screening in a 384-well format, enabling hit optimization and facilitating the discovery of inhibitors for MDA5, LGP2, and DDX1. Through DEL-ML screen, we identified a selective MDA5 inhibitor that can be used to further interrogate its role in AD pathogenesis, and serve as a chemical starting point for future drug discovery efforts. This ligand represents first-in-class small molecule inhibitor for MDA5, a target that has been underexplored in the context of its role in AD.

DDX10 contributes to the proliferation and invasion of DLBCL cells via positively regulating FBL, highlighting the DDX10-FBL axis as a potential therapeutic target. This work provides new insights into DLBCL pathogenesis and underscores the biomedical relevance of targeting DDX10-FBL.

Our findings uncover a novel mechanism by which DDX1 crotonylation regulates the AS of peroxisome-related genes and mediates peroxisomal redox homeostasis. This discovery bridges a critical gap in our understanding of how posttranslational modifications (PTMs) of DEAD/DEXD box RNA helicases modulate gene AS and identifies a potential therapeutic target for colorectal cancer.

The effects of DDX1 overexpression on cell proliferation, apoptosis, and lenvatinib resistance were significantly blocked by Ephrin-A3 knockdown. Mechanistically, DDX1 promotes lenvatinib resistance in HCC by regulating Ephrin-A3 mRNA stability and activating the Wnt/β-catenin pathway.  The increased DDX1 expression in HCC cells promotes lenvatinib resistance via regulating Ephrin-A3 mRNA stability and activating the Wnt/β-catenin pathway, indicating that targeting DDX1 may be an important strategy for overcoming lenvatinib resistance.

METTL3-mediated m6A modification stabilizes DDX17 to suppress EC cell proliferation, migration, and invasion through an IGF2BP2-dependent mechanism by inactivating the PI3K/AKT pathway.

TTD-specific variants in ERCC2/XPD result in TFIIH instability, altered interaction of the CAK with DDX1-SFPQ-NONO, and R-loop accumulation. Therefore, the limited amount of TFIIH that distinguishes TTD from XP gives rise to transcriptional stress and extensive gene expression deregulations, thus accounting for the wide spectrum of TTD clinical features.

Notably, through virtual screening, we identified a YTHDF2-specific small-molecule inhibitor. Therapeutic targeting of YTHDF2 with this inhibitor effectively suppresses protein translation in tumor cells and reverses paclitaxel resistance.

An in vivo xenograft assay further confirmed the therapeutic potential of compound 5o, demonstrating tumor growth inhibition rates of 60%, 78%, and 88% at doses of 5 mg/kg, 10 mg/kg, and 20 mg/kg, respectively. This study highlights a promising chemotherapeutic agent for the effective treatment of lung cancer.