Microarray analysis of miRNA expression profiles following whole body irradiation in a mouse model

Aryankalayil, Molykutty J.; Chopra, Sunita; Makinde, Adeola Y.; Eke, Iris; Levin, Joel; Shankavaram, Uma; MacMillan, Laurel; Vanpouille-Box, Claire; Demaria, Sandra; Coleman, C. Norman

doi:10.1080/1354750x.2018.1479771

Cited by 32 publications

(39 citation statements)

References 53 publications

(47 reference statements)

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“…Biomarkers to predict both acute and late adverse outcomes of radiation exposure are critically needed to identify individuals at risk after a radiological incident, especially since early therapeutic intervention can dramatically improve survival rates in the context of ARS [1][2][3][4][5][6], and perhaps late disease [2]. Efforts into monitoring changes in blood or plasma have yielded encouraging data and identified potential biomarkers of radiation exposure, including proteins [7][8][9][10], mRNA [11][12][13][14][15][16], non-coding RNA [17], and microRNA (miRNA) [18][19][20][21][22][23][24]. Because circulating miRNA are protected from degradation in extracellular vesicles or protein complexes, and are stable at room temperature for hours to days, they are exceptionally well suited for triage in the field [25].…”

Section: Introductionmentioning

confidence: 99%

“…miRNA can be released into extracellular biofluids, such as plasma, and may participate in cell-cell and tissue-tissue communication [27]. Changes in the circulating miRNA profile have been observed in pathophysiological conditions, such as cancer [28,29], and after exposure to radiation [18][19][20][21][22][23][24]. Since miRNA can be tissue-specific, the circulating miRNA profile may reflect what tissues are injured.…”

Section: Introductionmentioning

confidence: 99%

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Identification of miRNA signatures associated with radiation-induced late lung injury in mice

et al. 2020

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Acute radiation exposure of the thorax can lead to late serious, and even life-threatening, pulmonary and cardiac damage. Sporadic in nature, late complications tend to be difficult to predict, which prompted this investigation into identifying non-invasive, tissue-specific biomarkers for the early detection of late radiation injury. Levels of circulating microRNA (miRNA) were measured in C3H and C57Bl/6 mice after whole thorax irradiation at doses yielding approximately 70% mortality in 120 or 180 days, respectively (LD 70/120 or 180). Within the first two weeks after exposure, weight gain slowed compared to sham treated mice along with a temporary drop in white blood cell counts. 52% of C3H (33 of 64) and 72% of C57Bl/6 (46 of 64) irradiated mice died due to late radiation injury. Lung and heart damage, as assessed by computed tomography (CT) and histology at 150 (C3H mice) and 180 (C57Bl/6 mice) days, correlated well with the appearance of a local, miRNA signature in the lung and heart tissue of irradiated animals, consistent with inherent differences in the C3H and C57Bl/6 strains in their propensity for developing radiation-induced pneumonitis or fibrosis, respectively. Radiation-induced changes in the circulating miRNA profile were most prominent within the first 30 days after exposure and included miRNA known to regulate inflammation and fibrosis. Importantly, early changes in plasma miRNA expression predicted survival with reasonable accuracy (88-92%). The miRNA signature that predicted survival in C3H mice, including miR-34a-5p,-100-5p, and-150-5p, were associated with pro-inflammatory NF-κB-mediated signaling pathways, whereas the signature identified in C57Bl/6 mice (miR-34b-3p,-96-5p, and-802-5p) was associated with TGF-β/SMAD signaling. This study supports the hypothesis that plasma miRNA profiles could be used to identify individuals at high risk of organ-specific late radiation damage, with applications for radiation oncology clinical practice or in the context of a radiological incident.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Identification of miRNA signatures associated with radiation-induced late lung injury in mice

et al. 2020

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“…97 In a study published by our group in 2018, we reported the upregulation of miR-223-3p, let-7b-5p, and miR-574-5p and the downregulation of miR-140-5p, let-7f-5p, miR-150-5p, and the miR-17 family. 98 Using female C57BL/6 mice exposed to 2-15 Gy TBI, we observed a maximum number of miRNAs altered within the first 48 hours. 98 Additionally, an inverse correlation between miR-17 family members and their targets was observed and validated in non-human primates.…”

Section: Circrnas In Radiation Responsementioning

confidence: 86%

Long and short non-coding RNA and radiation response: a review

May

Bylicky

Chopra

et al. 2021

Translational Research

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This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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“…Microarray analysis was performed for sham animals (0 Gy) and 1 Gy, 2 Gy, 4 Gy, 8 Gy, and 12 Gy irradiated animals. Quality assessments and microarray experiments were completed as previously reported [47]. Samples were hybridized to Agilent Mouse GE 8 × 60K v2 arrays for mRNA expression analysis and to Agilent Mouse miRNA 8 × 60K v21.0 arrays (Design ID 070155) for miRNA expression analysis.…”

Section: Microarray Analysismentioning

confidence: 99%

“…However, there is limited research on understanding their role in normal tissue damage after radiation [38][39][40]. Our lab and others have identi ed alterations in lncRNA and miRNA at long and short time points post-radiation both in vivo and in vitro [41][42][43][44]. In a previous study, our laboratory demonstrated dose responsive upregulation in whole blood of damage induced noncoding lncRNA (Dino), plasmacytoma variant translocation 1 (Pvt1) and tumor protein P53 pathway corepressor 1 (Trp53cor1) in a whole-body irradiation mouse model [45].…”

Section: Introductionmentioning

confidence: 99%

Analysis of lncRNA-miRNA-mRNA Expression Pattern in Heart Tissue After Total Body Irradiation in a Mouse Model

Aryankalayil

Martello

Bylicky

et al. 2020

Preprint

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Background: Radiation therapy is integral to effective thoracic cancer treatments, but its application is limited by sensitivity of critical organs such as the heart. The impacts of acute radiation-induced damage and its chronic effects on normal heart cells are highly relevant in radiotherapy with increasing lifespans of patients. Biomarkers for normal tissue damage after radiation exposure, whether accidental or therapeutic, are being studied as indicators of both acute and delayed effects. Recent research has highlighted the potential importance of RNAs, including messenger RNAs (mRNAs), microRNAs (miRNAs), and long non-coding RNAs (lncRNAs) as biomarkers to assess radiation damage. Understanding changes in mRNA and non-coding RNA expression will elucidate biological pathway changes after radiation. Methods: To identify significant expression changes in mRNAs, lncRNAs, and miRNAs, we performed whole transcriptome microarray analysis of mouse heart tissue at 48h after whole-body irradiation with 1, 2, 4, 8, and 12 Gray (Gy). We also validated changes in specific lncRNAs through RT-qPCR. Ingenuity Pathway Analysis (IPA) was used to identify pathways associated with gene expression changes. Results: We observed sustained increases in lncRNAs and mRNAs, across all doses of radiation. Alas2, Aplnr, and Cxc3r1 were the most significantly downregulated mRNAs across all doses. Among the significantly upregulated mRNAs were cell-cycle arrest biomarkers Gdf15, Cdkn1a, and Ckap2. Additionally, IPA identified significant changes in gene expression relevant to senescence, apoptosis, hemoglobin synthesis, inflammation, and metabolism. LncRNAs Abhd11os, Pvt1, Trp53cor1, and Dino showed increased expression with increasing doses of radiation. We did not observe any miRNAs with sustained up- or downregulation across all doses, but miR-149-3p, miR-6538, miR-8101, miR-7118-5p, miR-211-3p, and miR-3960 were significantly upregulated after 12 Gy. Conclusions: Radiation-induced RNA expression changes may be predictive of normal tissue toxicities and may indicate targetable pathways for radiation countermeasure development and improved radiotherapy treatment plans.

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Microarray analysis of miRNA expression profiles following whole body irradiation in a mouse model

Abstract: Whole blood-based miRNA expression signatures might be used for predicting radiation exposures in a mass casualty nuclear incident.

Cited by 32 publications

References 53 publications

Identification of miRNA signatures associated with radiation-induced late lung injury in mice

Identification of miRNA signatures associated with radiation-induced late lung injury in mice

Long and short non-coding RNA and radiation response: a review

Analysis of lncRNA-miRNA-mRNA Expression Pattern in Heart Tissue After Total Body Irradiation in a Mouse Model

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