Meta-analysis using a novel database, miRStress, reveals miRNAs that are frequently associated with the radiation and hypoxia stress-responses.
Organisms are often exposed to environmental pressures that affect homeostasis, so it is important to understand the biological basis of stress-response. Various biological mechanisms have evolved to help cells cope with potentially cytotoxic changes in their environment. miRNAs are small non-coding RNAs which are able to regulate mRNA stability. It has been suggested that miRNAs may tip the balance between continued cytorepair and induction of apoptosis in response to stress. There is a wealth of data in the literature showing the effect of environmental stress on miRNAs, but it is scattered in a large number of disparate publications. Meta-analyses of this data would produce added insight into the molecular mechanisms of stress-response. To facilitate this we created and manually curated the miRStress database, which describes the changes in miRNA levels following an array of stress types in eukaryotic cells. Here we describe this database and validate the miRStress tool for analysing miRNAs that are regulated by stress. To validate the database we performed a cross-species analysis to identify miRNAs that respond to radiation. The analysis tool confirms miR-21 and miR-34a as frequently deregulated in response to radiation, but also identifies novel candidates as potentially important players in this stress response, including miR-15b, miR-19b, and miR-106a. Similarly, we used the miRStress tool to analyse hypoxia-responsive miRNAs. The most frequently deregulated miRNAs were miR-210 and miR-21, as expected. Several other miRNAs were also found to be associated with hypoxia, including miR-181b, miR-26a/b, miR-106a, miR-213 and miR-192. Therefore the miRStress tool has identified miRNAs with hitherto unknown or under-appreciated roles in the response to specific stress types. The miRStress tool, which can be used to uncover new insight into the biological roles of miRNAs, and also has the potential to unearth potential biomarkers for therapeutic response, is freely available at http://mudshark.brookes.ac.uk/MirStress.
Department of Biological and Medical Sciences, Oxford Brookes University, Oxford, United Kingdom.
Laura Ann
LA
Jacobs
Findlay
F
Bewicke-Copley
Mark Graham
MG
Poolman
Ryan Charles
RC
Pink
Laura Ann
LA
Mulcahy
Isabel
I
Baker
Ellie-May
EM
Beaman
Travis
T
Brooks
Daniel Paul
DP
Caley
William
W
Cowling
James Michael Stevenson
JM
Currie
Jessica
J
Horsburgh
Lottie
L
Kenehan
Emma
E
Keyes
Daniel
D
Leite
Davide
D
Massa
Adam
A
McDermott-Rouse
Priya
P
Samuel
Hannah
H
Wood
Munira
M
Kadhim
David Raul Francisco
DR
Carter
D015687:Cell Hypoxia / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D020871:RNA Stability / Q000235:genetics; D011827:Radiation
D035683:MicroRNAs