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RSS FeedsIJMS, Vol. 24, Pages 2761: Overexpression of Both Human Sodium Iodide Symporter (NIS) and BRG1-Bromodomain Synergistically Enhances Radioiodine Sensitivity by Stabilizing p53 through NPM1 Expression (International Journal of Molecular Sciences)

 
 

1 february 2023 10:41:43

 
IJMS, Vol. 24, Pages 2761: Overexpression of Both Human Sodium Iodide Symporter (NIS) and BRG1-Bromodomain Synergistically Enhances Radioiodine Sensitivity by Stabilizing p53 through NPM1 Expression (International Journal of Molecular Sciences)
 


Improved therapeutic strategies are required to minimize side effects associated with radioiodine gene therapy to avoid unnecessary damage to normal cells and radiation-induced secondary malignancies. We previously reported that codon-optimized sodium iodide symporter (oNIS) enhances absorption of I-131 and that the brahma-associated gene 1 bromodomain (BRG1-BRD) causes inefficient DNA damage repair after high-energy X-ray therapy. To increase the therapeutic effect without applying excessive radiation, we considered the combination of oNIS and BRG1-BRD as gene therapy for the most effective radioiodine treatment. The antitumor effect of I-131 with oNIS or oNIS+BRD expression was examined by tumor xenograft models along with functional assays at the cellular level. The synergistic effect of both BRG1-BRD and oNIS gene overexpression resulted in more DNA double-strand breaks and led to reduced cell proliferation/survival rates after I-131 treatment, which was mediated by the p53/p21 pathway. We found increased p53, p21, and nucleophosmin 1 (NPM1) in oNIS- and BRD-expressing cells following I-131 treatment, even though the remaining levels of citrulline and protein arginine deiminase 4 (PAD4) were unchanged at the protein level.


 
71 viewsCategory: Biochemistry, Biophysics, Molecular Biology
 
IJMS, Vol. 24, Pages 2768: Synthesis of Synthetic Musks: A Theoretical Study Based on the Relationships between Structure and Properties at Molecular Scale (International Journal of Molecular Sciences)
IJMS, Vol. 24, Pages 2771: Safety and Immunogenicity of a Chimeric Subunit Vaccine against Shiga Toxin-Producing Escherichia coli in Pregnant Cows (International Journal of Molecular Sciences)
 
 
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