Microarray analysis of miRNA expression profiles following whole body irradiation in a mouse model.
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ABSTRACT:
SUBMITTER: Aryankalayil MJ
PROVIDER: S-EPMC6982201 | biostudies-literature | 2018 Nov
REPOSITORIES: biostudies-literature
Publications
Microarray analysis of miRNA expression profiles following whole body irradiation in a mouse model.
Aryankalayil Molykutty J MJ Chopra Sunita S Makinde Adeola A Eke Iris I Levin Joel J Shankavaram Uma U MacMillan Laurel L Vanpouille-Box Claire C Demaria Sandra S Coleman C Norman CN
Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals 20180619 7
<h4>Context</h4>Accidental exposure to life-threatening radiation in a nuclear event is a major concern; there is an enormous need for identifying biomarkers for radiation biodosimetry to triage populations and treat critically exposed individuals.<h4>Objective</h4>To identify dose-differentiating miRNA signatures from whole blood samples of whole body irradiated mice.<h4>Methods</h4>Mice were whole body irradiated with X-rays (2 Gy-15 Gy); blood was collected at various time-points post-exposur ...[more]
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Project description:Recent reports have shown a link between radiation exposure and non-cancer diseases such as radiation-induced heart disease (RIHD). Radiation exposures are often inhomogeneous, and out-of-target effects have been studied in terms of cancer risk, but very few studies have been carried out for non-cancer diseases. Here, the role of miRNAs in the pathogenesis of RIHD was investigated. C57Bl/6J female mice were whole- (WBI) or partial-body-irradiated (PBI) with 2 Gy of X-rays or sham-irradiated (SI). In PBI exposure, the lower third of the mouse body was irradiated, while the upper two-thirds were shielded. From all groups, hearts were collected 15 days or 6 months post-irradiation. The MiRNome analysis at 15 days post-irradiation showed that miRNAs, belonging to the myomiR family, were highly differentially expressed in WBI and PBI mouse hearts compared with SI hearts. Raman spectral data collected 15 days and 6 months post-irradiation showed biochemical differences among SI, WBI and PBI mouse hearts. Fibrosis in WBI and PBI mouse hearts, indicated by the increased deposition of collagen and the overexpression of genes involved in myofibroblast activation, was found 6 months post-irradiation. Using an in vitro co-culture system, involving directly irradiated skeletal muscle and unirradiated ventricular cardiac human cells, we propose the role of miR-1/133a as mediators of the abscopal response, suggesting that miRNA-based strategies could be relevant for limiting tissue-dependent reactions in non-directly irradiated tissues.
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Project description:Long non-coding RNAs (lncRNAs) are emerging as key molecules in regulating many biological processes and have been implicated in development and disease pathogenesis. Biomarkers of cancer and normal tissue response to treatment are of great interest in precision medicine and for public health and medical management of disasters such as assessing radiation injury following accidental or intentional exposure. Circulating and functional RNAs, including microRNAs (miRNAs) and lncRNAs, in whole blood and other body fluids represent potential valuable candidates as biomarkers. Early prediction of possible acute, intermediate, and delayed effects of radiation exposure will enable timely therapeutic interventions. To address whether lncRNAs could serve as biomarkers for radiation bio-dosimetry, we performed whole genome transcriptome analysis in a mouse model after whole body irradiation. Differential lncRNA expression patterns were evaluated at 16-, 24-, and 48-hour time points post irradiation in total RNA isolated from whole blood of mice exposed to 1, 2, 4, 8, and 12 Gy of gamma-rays. Sham irradiated animals served as controls. Significant alterations in the expression patterns of lncRNAs were observed after different radiation doses at the various timepoints. We identified several lncRNAs known for DNA damage response as well as immune response as radiation induced biomarkers. Long non-coding RNA targets of tumor protein 53 (P53), Trp53cor1, Dino, Pvt1 and Tug1 and an upstream regulator of p53, Meg3 were altered in response to radiation. Gm14005 (Morrbid) and Tmevpg1 were regulated by radiation across all time points and doses. These two lncRNAs have important potential as blood based radiation biomarkers; Gm14005 (Morrbid) has recently been shown to play a key role in inflammatory response while Tmevpg1 has been implicated in the regulation of interferon-gamma. Precise molecular biomarkers will not only enable the development and effective use of medical countermeasures but also may be used to detect and circumvent or mitigate normal tissue injury in cancer radiotherapy treatments.
2018-05-31 | GSE104121 | GEO
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2022-06-06 | GSE202586 | GEO