Ting Shen | PubMed Health

PubMed2026

DDX21 Enhances Radiosensitivity in Head and Neck Squamous Cell Carcinoma by Suppressing MK2-Mediated DNA Damage Response.

Radioresistance remains a significant challenge in the radiotherapy (RT) of head and neck squamous cell carcinoma (HNSCC). However, the biological factors that govern sensitivity to this therapy are not well-understood. The DEAD-box family is known for its role in genome stability, and inextricably linked to the radiotherapy resistance of tumors. This study found the role of the RNA helicase DDX21 in regulating radiosensitivity through extensive data mining. High DDX21 expression predicted improved survival after postoperative radiotherapy. Overexpression of DDX21 increased radiosensitivity in vitro and in vivo, whereas depletion promoted radioresistance. In vitro, DDX21 enhanced radiation-induced DNA damage, genomic instability, and apoptosis by binding MK2 and suppressing MK2 phosphorylation independently of p38 activity. Meanwhile MK2 inhibition restored and further augmented radiosensitivity in DDX21-deficient cells and xenografts by increasing DNA damage and apoptosis. Overall, DDX21 regulates radiosensitivity in HNSCC by suppressing MK2 signaling and modulating the radiation-induced DNA damage response. Its expression may serve as a potential biomarker associated with radiosensitivity, and MK2 inhibition offers a promising approach to overcome radioresistance in tumors with low DDX21 expression.

DDX21↗

PubMed2026

Multilevel genomic, transcriptomic, and epidemiologic evidence linking diabetic retinopathy to Alzheimer disease.

BACKGROUND: Diabetic retinopathy (DR) and Alzheimer disease (AD) share metabolic and vascular dysfunctions, but the extent to which they reflect overlapping genetic susceptibility and neurovascular-metabolic regulatory pathways remains unclear. We combined multi-omics analyses with population-based data to examine the genetic convergence, cellular pathways, and longitudinal association between DR and AD. METHODS: We performed a two-sample Mendelian randomisation (MR) to estimate the association between genetically predicted DR liability and AD risk. We used Bayesian colocalisation analysis to identify shared genomic loci, and summary-data-based MR (SMR) to detect expression-mediated genes jointly associated with DR and AD. We analysed single-cell RNA sequencing data to characterise shared cellular features and related biological pathways. We also conducted an MR-based mediation analysis to explore whether lipid-related, metabolic, or inflammatory traits mediated the observed DR-AD association, and a longitudinal analysis of the UK Biobank cohort to assess the association between DR and incident AD. RESULTS: With the MR analysis, we found that genetically predicted liability to DR was associated with a modest increase in AD risk. Colocalisation analysis supported a shared genetic signal. We identified three genes with shared expression-mediated associations across DR and AD through SMR. Functional enrichment analyses revealed partially overlapping neurovascular and metabolic pathways. Using MR-based mediation analysis, we found no significant intermediary traits linking DR and AD. Findings from the UK Biobank cohort were directionally consistent with the genetic analyses. CONCLUSIONS: Genetic liability to DR is associated with an increased risk of AD and is accompanied by shared expression-mediated effects and convergent neurovascular-metabolic pathways. These findings support the possibility that DR may serve as a clinically accessible indicator of increased neurodegenerative vulnerability.

Humans↗