NASA Logo

NTRS

NTRS - NASA Technical Reports Server

Back to Results
Comparative MicroRNA Expression Patterns in Fibroblasts after Low and High Doses of Low-LET Radiation ExposureExposure to ionizing radiation causes DNA damage to cells, and provokes a plethora of cellular responses controlled by unique gene-directed signaling pathways. MicroRNAs (miRNAs) are small (~22-nucleotide), non-coding RNAs which functionally silence gene expression by either degrading the messages or inhibiting translation. Here we investigate radiation-dependent changes in these negative regulators by comparing the expression patterns of all 462 known human miRNAs in fibroblasts, after exposure to low (0.1 Gy) or high (2 Gy) doses of X-rays at 30 min, 2, 6 and 24 hrs post-treatment. The expression patterns of microRNAs after low and high doses of radiation show a similar qualitative down-regulation trend at early (0.5 hr) and late (24 hr) time points, with a quantitatively steeper slope following the 2 Gy exposures. Interestingly, an interruption of this downward trend is observed after the 2 Gy exposure, i.e. a significant up-regulation of microRNAs at 2 hrs, then reverting to the downward trend by 6 hrs; this interruption at the intermediate time point was not observed with the 0.1 Gy exposure. At the early time point (0.5 hr), candidate gene targets of selected down-regulated microRNAs, common to both 0.1 and 2 Gy exposures, were those functioning in chromatin remodeling. Candidate target genes of unique up-regulated microRNAs seen at a 2 hr intermediate time point, after the 2 Gy exposure only, are those involved in cell death signaling. Finally, putative target genes of down-regulated microRNAs seen at the late (24 hr) time point after either doses of radiation are those involved in the up-regulation of DNA repair, cell signaling and homeostasis. Thus we hypothesize that after radiation exposure, microRNAs acting as hub negative regulators for unique signaling pathways needed to be down-regulated so as to de-repress their target genes for the proper cellular responses, including DNA repair and cell maintenance. The unique microRNAs up-regulated at 2 hr after 2 Gy suggest the cellular response to functionally suppress the apoptotic death signaling reflex after exposure to high dose radiation. Further analyses with transcriptome and global proteomic profiling will validate the reciprocal expression of signature microRNAs selected in our radiation-exposed cells, and their candidate target gene families, and test our hypothesis that unique radiation-specific microRNAs are keys in governing signaling responses for damage control of this environmental hazard.
Document ID
20070022351
Acquisition Source
Johnson Space Center
Document Type
Conference Paper
Authors
Maes, Olivier C.
(Louisville Univ. KY, United States)
Xu, Suying
(Louisville Univ. KY, United States)
Hada, Megumi
(NASA Johnson Space Center Houston, TX, United States)
Wu, Honglu
(NASA Johnson Space Center Houston, TX, United States)
Wang, Eugenia
(Louisville Univ. KY, United States)
Date Acquired
August 23, 2013
Publication Date
July 13, 2007
Subject Category
Life Sciences (General)
Meeting Information
Meeting: 18th Annual NASA Space Radiation Investigators'' Workshop
Location: Rohnert Park, CA
Country: United States
Start Date: July 13, 2007
End Date: July 15, 2007
Sponsors: Universities Space Research Association
Distribution Limits
Public
Copyright
Other

Available Downloads

There are no available downloads for this record.
No Preview Available