f apoptosis after irradiation in ARRB1- and TXN1knockdown cells. Depletion of HSPA9 increased the level of 5 miR-525-3p Mediated Survival after Irradiation doi: 10.1371/journal.pone.0077484.g001 6 miR-525-3p Mediated Survival after Irradiation doi: 10.1371/journal.pone.0077484.g002 radiation-induced apoptosis, while reduction of hnRNP K had no impact. Taken together, these Chebulinic acid site results demonstrate that cell survival after irradiation is dependent on the coordinated miR-525-3p-mediated translational repression of both anti-survival and pro-survival targets. Discussion Ionizing radiation induces changes in miRNA expression in a range of cell types. The subsequent cellular responses can often be reiterated through the manipulation of a single miRNA species. However, the mechanisms by which the miRNA changes modulate radiation sensitivity remain largely unknown with an almost complete lack of evidence identifying the protein 26574517 targets that are actually regulated by radiation-responsive miRNAs. Recently, we demonstrated that a radiation-induced increase in miR-525-3p is sufficient to limit the extent of cell death and apoptosis in human endothelial cells. In the current study we now show that radiation-induced up-regulation of miR-525-3p occurs in a variety of other human cell lines, where it is essential for sustaining cell survival. The consistency of this function across multiple cell types suggests a conserved and important role of miR-525-3p in regulating the radiation response. This is in sharp contrast to the more restricted, cell type specific, roles suggested for other radiation-regulated miRNAs. Our proteomic analysis identified 14 proteins that were repressed by the radiation-induced increase in miR-525-3p. The overall changes in protein expression were subtle, in accordance with the suggested role of miRNAs as fine tuners of protein abundance. Gene ontology annotation assigned the majority of the deregulated proteins to the biological process of cell death and apoptosis. This is in accordance with previous data describing radiation-induced apoptosis as one of the most important radiation-response pathways in endothelial cells. It is also in agreement to our earlier experimental data showing an impaired increase in apoptosis induction in cells where the radiation-induced increase in miR-525-3p was blocked. A number of the most important nodal molecules predicted by Ingenuity Pathway Analysis of the deregulated proteins are implicated in radiation-induced apoptosis. For example RELA, encodes the p65 protein that is a component of the NFB complex activated by radiation to influence apoptosis and DNA repair. The nodal molecule p53 is stabilized after radiation exposure and can induce the expression of multiple genes involved in apoptosis. 26574517 ERK-mediated signals and Bcl-2 both inhibit radiation-induced changes in the mitochondrial membrane and the subsequent cell death in lymphocytic leukemia cells. Bcl-2 is an important protein in apoptosis whose 7 miR-525-3p Mediated Survival after Irradiation doi: 10.1371/journal.pone.0077484.g003 8 miR-525-3p Mediated Survival after Irradiation doi: 10.1371/journal.pone.0077484.g004 9 miR-525-3p Mediated Survival after Irradiation doi: 10.1371/journal.pone.0077484.g005 suppression renders cells more susceptible to radiationinduced 
apoptosis. The nodal molecule MYC has a role in sensitizing cells to apoptosis, with inhibition of MYC by antisense oligonucleotides reducing radiation-induced apoptosis in a sma