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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Apr 10, 2012 |
| Title |
Gene expression profiling of PBL in response to ionising radiation and modeled microgravity |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
BACKGROUND:
Ionizing radiation (IR) can be extremely harmful for human cells since an improper DNA-damage response (DDR) to IR can contribute to carcinogenesis initiation. Perturbations in DDR pathway can originate from alteration in the functionality of the microRNA-mediated gene regulation, being microRNAs (miRNAs) small noncoding RNA that act as post-transcriptional regulators of gene expression. In this study we gained insight into the role of miRNAs in the regulation of DDR to IR under microgravity, a condition of weightlessness experienced by astronauts during space missions, which could have a synergistic action on cells, increasing the risk of radiation exposure.
METHODOLOGY/PRINCIPAL FINDINGS:
We analyzed miRNA expression profile of human peripheral blood lymphocytes (PBL) incubated for 4 and 24 h in normal gravity (1 g) and in modeled microgravity (MMG) during the repair time after irradiation with 0.2 and 2Gy of γ-rays. Our results show that MMG alters miRNA expression signature of irradiated PBL by decreasing the number of radio-responsive miRNAs. Moreover, let-7i*, miR-7, miR-7-1*, miR-27a, miR-144, miR-200a, miR-598, miR-650 are deregulated by the combined action of radiation and MMG. Integrated analyses of miRNA and mRNA expression profiles, carried out on PBL of the same donors, identified significant miRNA-mRNA anti-correlations of DDR pathway. Gene Ontology analysis reports that the biological category of "Response to DNA damage" is enriched when PBL are incubated in 1 g but not in MMG. Moreover, some anti-correlated genes of p53-pathway show a different expression level between 1 g and MMG. Functional validation assays using luciferase reporter constructs confirmed miRNA-mRNA interactions derived from target prediction analyses.
CONCLUSIONS/SIGNIFICANCE:
On the whole, by integrating the transcriptome and microRNome, we provide evidence that modeled microgravity can affects the DNA-damage response to IR in human PBL.
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| Overall design |
Gene expression signature was defined in PBL irradiated with gamma-rays (2.0 Gy) and incubated in modeled microgravity (mmg) and in parallel ground conditions (1g) for 24h. Five independent experiments were performed for each donor to address wich mRNAs were regulated on IR stress. The level of each transcript was represented as Log2.
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| Contributor(s) |
Girardi C, De Pittà C, Casara S, Sales G, Lanfranchi G, Celotti L, Mognato M |
| Citation(s) |
22347458 |
| Submission date |
Feb 03, 2010 |
| Last update date |
Jan 23, 2019 |
| Contact name |
Gerolamo Lanfranchi |
| E-mail(s) |
stefano.cagnin@unipd.it
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| Phone |
+39-0498276219
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| Organization name |
University of Padova
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| Department |
CRIBI - Biotechnology Center and Biology Department
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| Lab |
Functional Genomics Lab
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| Street address |
Via U. Bassi, 58/B
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| City |
Padova |
| ZIP/Postal code |
35131 |
| Country |
Italy |
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| Platforms (1) |
| GPL6480 |
Agilent-014850 Whole Human Genome Microarray 4x44K G4112F (Probe Name version) |
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| Samples (20)
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| Relations |
| BioProject |
PRJNA125639 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE20173_RAW.tar |
94.8 Mb |
(http)(custom) |
TAR (of TXT) |
| Processed data included within Sample table |
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