Meta-Analysis Using a Novel Database, miRStress, Reveals miRNAs That Are Frequently Associated with the Radiation and Hypoxia Stress-Responses

Abstract

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.

Characteristic MicroRNA Expression Induced by δ-Opioid Receptor Activation in the Rat Liver Under Prolonged Hypoxia

“…MiR-107-3p inhibition can reduce capillary density in the ischemic boundary zone after stroke and regulates post-stroke angiogenesis by targeting Dicer1 [52]. MiR-192-5p is also a hypoxia responsive miRNA under different cellular stress [53]. miR-204-5p promotes the apoptosis of neuronal cells under hypoxia by targeting Bcl-2 [54].…”

Cisplatin induces the release of extracellular vesicles from ovarian cancer cells that can induce invasiveness and drug resistance in bystander cells

“…They can be found in various body fluids and in the tumour microenvironment and can transmit messages to neighbouring cells as well as to distant cells (17,18). miRNAs, short non-coding RNAs whose levels can be altered during stress response (19), can also be shuttled between cells in the tumour microenvironment via EVs. Extracellular vesicles have been shown to modulate numerous factors in tumour cells including proliferation (20), viability (21) and metastatic capability (22).…”

Interdigital tissue remodelling in the embryonic limb involves dynamic regulation of the miRNA profiles

“…This miRNA belongs to a group of miRNAs that coordinate the molecular mechanisms activated in the cells in response to environmental stress, termed miRStress (Jacobs et al. ) and actively participates in the differentiation of avian germ cells (Lee et al. ).…”

“…Other miRNAs, present in the miRStress database are also expressed during the course of interdigit regression, including miR‐181b, miR‐21 and miR‐106 (Jacobs et al. ) but, except for miR‐21, they are not upregulated during interdigit regression.…”