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Gene expression profiling of PBL in response to ionising radiation and modeled microgravity

Metadata Updated: December 6, 2023

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 gamma-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. 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 which mRNAs were regulated on IR stress. The level of each transcript was represented as Log2.

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Public: This dataset is intended for public access and use. License: us-pd

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Metadata Created Date January 31, 2023
Metadata Updated Date December 6, 2023
Data Update Frequency irregular

Metadata Source

Harvested from NASA Data.json

Additional Metadata

Resource Type Dataset
Metadata Created Date January 31, 2023
Metadata Updated Date December 6, 2023
Publisher National Aeronautics and Space Administration
Identifier nasa_genelab_GLDS-129_84ea-fpze
Data First Published 2021-05-21
Data Last Modified 2023-01-26
Category Earth Science
Public Access Level public
Data Update Frequency irregular
Bureau Code 026:00
Metadata Context
Metadata Catalog ID
Schema Version
Catalog Describedby
Harvest Object Id 893909a0-f28f-40b9-8785-5682046b00da
Harvest Source Id 58f92550-7a01-4f00-b1b2-8dc953bd598f
Harvest Source Title NASA Data.json
Homepage URL
Program Code 026:005
Source Datajson Identifier True
Source Hash b7c4d9909d1dbe295ca8c0f4754b4a0cbc04b5ef7b736280e02baf8d6993287c
Source Schema Version 1.1

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