Ionizing Radiation-Induced Oxidative Stress Alters miRNA Expression

Abstract

BackgroundMicroRNAs (miRNAs) are small, highly conserved, non-coding RNA that alter protein expression and regulate multiple intracellular processes, including those involved in the response to cellular stress. Alterations in miRNA expression may occur following exposure to several stress-inducing anticancer agents including ionizing radiation, etoposide, and hydrogen peroxide (H2O2).Methodology/Principal FindingsNormal human fibroblasts were exposed to radiation, H2O2, or etoposide at doses determined by clonogenic cell survival curves. Total RNA was extracted and miRNA expression was determined by microarray. Time course and radiation dose responses were determined using RT-PCR for individual miRNA species. Changes in miRNA expression were observed for 17 miRNA species following exposure to radiation, 23 after H2O2 treatment, and 45 after etoposide treatment. Substantial overlap between the miRNA expression changes between agents was observed suggesting a signature miRNA response to cell stress. Changes in the expression of selected miRNA species varied in response to radiation dose and time. Finally, production of reactive oxygen species (ROS) increased with increasing doses of radiation and pre-treatment with the thiol antioxidant cysteine decreased both ROS production and the miRNA response to radiation.ConclusionsThese results demonstrate a common miRNA expression signature in response to exogenous genotoxic agents including radiation, H2O2, and etoposide. Additionally, pre-treatment with cysteine prevented radiation-induced alterations in miRNA expression which suggests that miRNAs are responsive to oxidative stress. Taken together, these results imply that miRNAs play a role in cellular defense against exogenous stress and are involved in the generalized cellular response to genotoxic oxidative stress.

TBHP-induced oxidative stress alters microRNAs expression in mouse testis

“…The change of miRNAs expression in response to oxidative stress has been investigated in different cells and tissue samples such as human fibroblasts and vascular and adipose tissues [48,23]. However, the effect of TBHP-induced oxidative stress on miRNA expression has not been investigated in mouse testis so far.…”

“…Alterations in miRNAs expression may occur following exposure to stress-generating agents. Simone's in vitro study on human fibroblast indicated that miRNAs may play a role in cellular defense against oxidative stress [48]. Nonetheless, there are limited studies to demonstrate the role and function of miRNAs in testis tissue and their relationship with male infertility.…”

miR-214 protects erythroid cells against oxidative stress by targeting ATF4 and EZH2

“…A number of previous studies demonstrated that the expression changes for certain miRNAs could be attributed to increased ROS production [45][46][47][48]. To elucidate the mechanism responsible for miR-214 down regulation in erythroid cells in response to stress, we investigated the relationship between miR-214 expression and ROS production.…”

“…EZH2 is the catalytic core component of PRC2 complex which conducts tri-methylation reaction at lysine 27 (K27) of histone 3 (H3), resulting in increased level of H3K27me3 [61,62]. Fine-tuned regulation of EZH2 is closely implicated in cell proliferation, differentiation, senescence and apoptosis under normal settings; however, deregulated EZH2 is associated with a number of disorders including various cancers [48,54]. To this end, we here tested the hypothesis that EZH2 could be a downstream target of Nrf2-miR-214 in erythroid cells against exotic stress.…”

2188 Prognostic role of the LCS-6 KRAS variant in locally advanced rectal cancer: Results of the EXPERT-C trial

“…when increasing let-7a or let-7b levels) or radio-resistance (i.e. when reducing let-7 g levels) in RAS mutant pancreatic and lung cancer cell lines [22][23][24]. We acknowledge that our results are hypothesis-generating.…”