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KDM5 family of demethylases promotes CD44-mediated chemoresistance in pancreatic adenocarcinomas. | LitMetric

AI Article Synopsis

  • Research indicates that the KDM5 family of histone demethylases is linked to drug resistance in cancer, particularly in pancreatic ductal adenocarcinoma (PDAC).
  • A comprehensive analysis showed that higher levels of KDM5A/C are found in gemcitabine-resistant PDAC cells, and manipulating their expression affects drug resistance and cell invasiveness.
  • The KDM5 family also interacts with stem cell marker CD44 and is involved in key oncogenic pathways, making them potential targets for therapy and biomarkers in PDAC treatment.

Article Abstract

A growing body of evidence suggests that the histone demethylase-lysine demethylase 5 (KDM5) family is associated with drug resistance in cancer cells. However, it is still not clear whether KDM5 family members promote chemotherapy resistance in pancreatic ductal adenocarcinomas (PDAC). Comprehensive bioinformatics analysis was performed to investigate the prognostic value, and functional mechanisms of KDM5 family members in PDAC. The effects of KDM5 family members on drug resistance in PDAC cells and the relationship with CD44, as a stem cell marker, were explored by gene knockout and overexpression strategies. Finally, our findings were validated by functional experiments such as cell viability, colony formation and invasion assays. We found that the expression of KDM5A/C was significantly higher in gemcitabine-resistant cells than in sensitive cells, consistent with the analysis of the GSCALite database. The knockdown of KDM5A/C in PDAC cells resulted in diminished drug resistance, less cell colonies and reduced invasiveness, while KDM5A/C overexpression showed the opposite effect. Of note, the expression of KDM5A/C changed accordingly with the knockdown of CD44. In addition, members of the KDM5 family function in a variety of oncogenic pathways, including PI3K/AKT and Epithelial-Mesenchymal Transition. In conclusion, KDM5 family members play an important role in drug resistance and may serve as new biomarkers or potential therapeutic targets in PDAC patients.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10600175PMC
http://dx.doi.org/10.1038/s41598-023-44536-2DOI Listing

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