Ionizing radiation-induced altered microRNA expression as biomarkers for assessing acute radiation injury

Singh, Vijay K.; Pollard, Harvey B.

doi:10.1080/14737159.2017.1366316

Cited by 26 publications

(18 citation statements)

References 15 publications

(18 reference statements)

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“…Curating microRNAs as radiation markers has been gaining significant traction in recent years 13,[34][35][36] . The small endogenous RNA theoretically modulates up to 30% of the entire human genome and thereby regulates a wide variety of cellular and molecular functions.…”

Section: Discussionmentioning

confidence: 99%

microRNA and Metabolite Signatures Linked to Early Consequences of Lethal Radiation

Chakraborty

Gautam

Holmes-Hampton

et al. 2020

Sci Rep

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Lethal total body irradiation (TBI) triggers multifactorial health issues in a potentially short time frame. Hence, early signatures of TBI would be of great clinical value. Our study aimed to interrogate microRnA (miRNA) and metabolites, two biomolecules available in blood serum, in order to comprehend the immediate impacts of TBI. Mice were exposed to a lethal dose (9.75 Gy) of Cobalt-60 gamma radiation and euthanized at four time points, namely, days 1, 3, 7 and 9 post-TBI. Serum miRNA libraries were sequenced using the Illumina small RNA sequencing protocol, and metabolites were screened using a mass spectrometer. The degree of early impacts of irradiation was underscored by the large number of miRNAs and metabolites that became significantly expressed during the Early phase (day 0 and 1 post-TBI). Radiation-induced inflammatory markers for bone marrow aplasia and pro-sepsis markers showed early elevation with longitudinal increment. Functional analysis integrating miRNA-proteinmetabolites revealed inflammation as the overarching host response to lethal TBI. Early activation of the network linked to the synthesis of reactive oxygen species was associated with the escalated regulation of the fatty acid metabolism network. In conclusion, we assembled a list of time-informed critical markers and mechanisms of significant translational potential in the context of a radiation exposure event.

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Section: Discussionmentioning

confidence: 99%

microRNA and Metabolite Signatures Linked to Early Consequences of Lethal Radiation

Chakraborty

Gautam

Holmes-Hampton

et al. 2020

Sci Rep

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“…Though there are several biomarkers validated/qualified by the US FDA for other indications, there are no FDA qualified biomarkers for any radiation-induced injury or for the response to countermeasures used to mitigate radiation-induced injury. There are numerous reasons for this [80,106], making approval of new radiation countermeasures somewhat difficult. On a positive note, the mechanism of action of this countermeasure and its cellular receptor have been well-documented.…”

Section: Expert Opinionmentioning

confidence: 99%

BIO 300: a promising radiation countermeasure under advanced development for acute radiation syndrome and the delayed effects of acute radiation exposure

Singh

Seed²

2020

Expert Opinion on Investigational Drugs

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Introduction: There are no radioprotectors currently approved by the United States Food and Drug Administration (US FDA) for either the hematopoietic acute radiation syndrome (H-ARS) or for the acute radiation gastrointestinal syndrome (GI-ARS). There are currently, however, three US FDA-approved medicinals that serve to mitigate acute irradiation-associated hematopoietic injury. Area covered: We present the current status of a promising radiation countermeasure, BIO 300 (a genistein-based agent), that has been extensively investigated in murine models of H-ARS and models of the delayed effects of acute radiation exposure (DEARE) and is currently being evaluated in large animal models. It is also being developed for the prevention of radiation-induced toxicities associated with solid tumor radiotherapy and is the subject of two active Investigational New Drug (IND) applications. We have included a listing and brief review of significant investigations of this promising medical countermeasure. Expert opinion: BIO 300 is a leading radioprotector under advanced development for H-ARS and DEARE, as well as for select oncologic indication(s). Efficacy following oral administration (po), lack of clinical side effects, storage at ambient temperature, and intended dual use makes BIO 300 an ideal candidate for military and civilian use as well as for storage in the Strategic National Stockpile.

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“…2,3 Therefore, there is a great need to identify radiationspecific biomarkers that are capable of identifying the radiation dose immediately after exposure to provide selected patients with appropriate treatment or palliative care. [4][5][6] The search for radiation exposure biomarkers relies on a 2-pronged approach. The first one, which is animal model based, is prospective, carefully controlled studies that are performed predominantly on mice and nonhuman primates (NHPs), in which total body irradiation with high, potentially lethal doses is used.…”

Section: Introductionmentioning

confidence: 99%

Circulating microRNAs as Biomarkers of Radiation Exposure: A Systematic Review and Meta-Analysis

Małachowska

Tomasik

Stawiski

et al. 2020

International Journal of Radiation Oncology*Biology*Physics

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Purpose: MicroRNAs (miRNAs) were hypothesized to be robust and easily measured biomarkers of radiation exposure, which has led to multiple studies in various clinical and experimental scenarios. We sought to identify evolutionary conserved, radiation-induced circulating miRNAs through a multispecies, integrative systematic review and meta-analysis of miRNAs in radiation. Methods and Materials: The systematic review was registered in the PROSPERO database (ID: 81701). We downloaded a list of studies with the query: (circulating OR plasma OR serum) AND (miRNA or microRNA) AND (radiat* OR radiotherapy OR irradiati*) from MEDLINE (103 studies), EMBASE (364 studies), and Cochrane Database of Systematic Reviews (0 studies). After deleting 116 duplicates, the remaining 351 abstracts were reviewed. Inclusion criteria were experimental study; human, mice, rat or nonhuman primate study; and serum or plasma miRNA expression measured before and after radiation exposure. Results: The screening procedure yielded 62 research studies. After verification, 30 articles contained data on miRNA expression change after irradiation. Thus, we obtained a database of 131 miRNAs from 96 pairwise post-/preirradiation comparisons reporting 2508 fold changes (FCs) of circulating miRNAs. The meta-analysis showed 28 miRNAs with significant radiation-induced change of their expression in the serum. In metaregression analysis, 7 miRNAsdmiR-150 (FC Z 0.40; 95% confidence interval [CI], 0.35-0.45), miR-29a (FC Z 0.87; 95% CI, 0.79-0.96), miR-29b (FC Z 0.85; 95% CI,

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Ionizing radiation-induced altered microRNA expression as biomarkers for assessing acute radiation injury

Cited by 26 publications

References 15 publications

microRNA and Metabolite Signatures Linked to Early Consequences of Lethal Radiation

microRNA and Metabolite Signatures Linked to Early Consequences of Lethal Radiation

BIO 300: a promising radiation countermeasure under advanced development for acute radiation syndrome and the delayed effects of acute radiation exposure

Circulating microRNAs as Biomarkers of Radiation Exposure: A Systematic Review and Meta-Analysis

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