RRC ID 69581
Author Sato Y, Yoshino H, Kashiwakura I, Tsuruga E.
Title DAP3 Is Involved in Modulation of Cellular Radiation Response by RIG-I-Like Receptor Agonist in Human Lung Adenocarcinoma Cells.
Journal Int J Mol Sci
Abstract Retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs) mediate anti-viral response through mitochondria. In addition, RLR activation induces anti-tumor effects on various cancers. We previously reported that the RLR agonist Poly(I:C)-HMW/LyoVec™ (Poly(I:C)) enhanced radiosensitivity and that cotreatment with Poly(I:C) and ionizing radiation (IR) more than additively increased cell death in lung adenocarcinoma cells, indicating that Poly(I:C) modulates the cellular radiation response. However, it remains unclear how mitochondria are involved in the modulation of this response. Here, we investigated the involvement of mitochondrial dynamics and mitochondrial ribosome protein death-associated protein 3 (DAP3) in the modulation of cellular radiation response by Poly(I:C) in A549 and H1299 human lung adenocarcinoma cell lines. Western blotting revealed that Poly(I:C) decreased the expression of mitochondrial dynamics-related proteins and DAP3. In addition, siRNA experiments showed that DAP3, and not mitochondrial dynamics, is involved in the resistance of lung adenocarcinoma cells to IR-induced cell death. Finally, we revealed that a more-than-additive effect of cotreatment with Poly(I:C) and IR on increasing cell death was diluted by DAP3-knockdown because of an increase in cell death induced by IR alone. Together, our findings suggest that RLR agonist Poly(I:C) modulates the cellular radiation response of lung adenocarcinoma cells by downregulating DAP3 expression.
Volume 22(1)
Published 2021-1-3
DOI 10.3390/ijms22010420
PII ijms22010420
PMID 33401559
PMC PMC7795940
MeSH Adenocarcinoma of Lung / drug therapy Adenocarcinoma of Lung / metabolism Adenocarcinoma of Lung / pathology* Adenocarcinoma of Lung / radiotherapy Apoptosis Apoptosis Regulatory Proteins / genetics Apoptosis Regulatory Proteins / metabolism* Cell Proliferation DEAD Box Protein 58 Gene Expression Regulation, Neoplastic* Humans Lung Neoplasms / drug therapy Lung Neoplasms / metabolism Lung Neoplasms / pathology* Lung Neoplasms / radiotherapy Poly I-C / pharmacology* RNA-Binding Proteins / genetics RNA-Binding Proteins / metabolism* Radiation, Ionizing* Receptors, Immunologic / agonists* Tumor Cells, Cultured
IF 4.556
Human and Animal Cells A549(RCB0098)