DAP3 Is Involved in Modulation of Cellular Radiation Response by RIG-I-Like Receptor Agonist in Human Lung Adenocarcinoma Cells.
Adenocarcinoma of Lung
/ drug therapy
Apoptosis
Apoptosis Regulatory Proteins
/ genetics
Cell Proliferation
DEAD Box Protein 58
Gene Expression Regulation, Neoplastic
Humans
Lung Neoplasms
/ drug therapy
Poly I-C
/ pharmacology
RNA-Binding Proteins
/ genetics
Radiation, Ionizing
Receptors, Immunologic
/ agonists
Tumor Cells, Cultured
death-associated protein 3
ionizing radiation
lung adenocarcinoma
mitochondria
radiosensitivity
retinoic acid-inducible gene-I-like receptor
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
03 Jan 2021
03 Jan 2021
Historique:
received:
15
12
2020
revised:
28
12
2020
accepted:
30
12
2020
entrez:
6
1
2021
pubmed:
7
1
2021
medline:
26
3
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 33401559
pii: ijms22010420
doi: 10.3390/ijms22010420
pmc: PMC7795940
pii:
doi:
Substances chimiques
Apoptosis Regulatory Proteins
0
DAP3 protein, human
0
RNA-Binding Proteins
0
Receptors, Immunologic
0
RIGI protein, human
EC 3.6.1.-
DEAD Box Protein 58
EC 3.6.4.13
Poly I-C
O84C90HH2L
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Japan Society for the Promotion of Science
ID : JP18K07623
Organisme : Takeda Science Foundation
ID : N/A
Organisme : Hirosaki University Grant for Exploratory Research by Young Scientists
ID : N/A
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