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Series GSE163133 Query DataSets for GSE163133
Status Public on Dec 14, 2020
Title Exosome-mediated radiosensitizing effect on neighboring cancer cells via exosomal microRNA
Organism Homo sapiens
Experiment type Non-coding RNA profiling by array
Summary The precise mechanism of intercellular communication among cancer cells after radiation exposure remains unclear. Exosomes are membrane-enclosed small vesicles constituted by lipid bilayers and are recognized as mediators of intercellular communication that transport a variety of intracellular components, including microRNA (miRNA). Here we identified novel roles of exosomes released from irradiated cells to neighboring cancer cells. To confirm the presence of exosomes in the culture media of the human pancreatic cancer cell line MIAPaCa-2, ultracentrifugation was performed followed by transmission electron microscopy and nanoparticle tracking analysis (NanoSight) using the exosome-specific surface markers CD9 and CD63. Subsequent endocytosis of exosomes was confirmed by fluorescent microscopy. Cell survival after irradiation and following the addition of exosomes was evaluated by a colony-forming assay. Expression of miRNAs in exosomes was then quantified by microarray analysis, while those of Cu/Zn superoxide dismutase (SOD1) and Mn-superoxide dismutase (SOD2) enzymes in MIAPaCa-2 cells were evaluated by western blotting. Results showed that the uptake of irradiated exosomes was significantly higher than that of non-irradiated exosomes. Notably, irradiated exosomes induced higher intracellular levels of ROS and a higher frequency of DNA damage in MIAPaCa-2 cells, as determined by fluorescent microscopy and immunocytochemistry, respectively. Moreover, six upregulated and five downregulated miRNAs were identified in 5 Gy- and 8 Gy-irradiated cells using miRNA microarray analyses. Further analyses using miRNA-mimics and real time reverse transcription PCR identified miR-6823-5p as a possible candidate for SOD1 inhibition, leading to increased intracellular ROS level and DNA damage. This is the first study to demonstrate that irradiated exosomes can enhance the radiation effect via increased intracellular ROS levels in cancer cells, potentially leading to improved understanding of the bystander effect of neighboring cancer cells.
Overall design To investigate which exosomal microRNAs are related to radiosensitizing effect, we extracted exomal RNA from non-irradiated cells and irradiated (5 Gy and 8 Gy) cells and compared a total of 2565 microRNAs expressions.
Contributor(s) Nakaoka A, Nakahana M, Inubushi S, Akasaka H, Salah M, Fujita Y, Kubota H, Hassan M, Nishikawa R, Mukumoto N, Ishihara T, Miyawaki D, Sasayama T, Sasaki R
Citation(s) 33649776
Submission date Dec 14, 2020
Last update date Apr 07, 2021
Contact name Satoshi Kondo
Organization name Toray Industries,Inc.
Street address 10-1 tebiro 6-chome
City Kamakura
State/province Kanagawa
ZIP/Postal code 248-8555
Country Japan
Platforms (1)
GPL21263 3D-Gene Human miRNA V21_1.0.0
Samples (3)
GSM4972444 0 GyExo
GSM4972445 5 GyExo
GSM4972446 8 GyExo
BioProject PRJNA685042

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE163133_RAW.tar 200.0 Kb (http)(custom) TAR (of TXT)
Raw data provided as supplementary file
Processed data included within Sample table

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