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Analysis of lncRNA-miRNA-mRNA expression pattern in heart tissue after total body radiation in a mouse model
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Analysis of lncRNA-miRNA-mRNA expression pattern in heart tissue after total body radiation in a mouse model
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Analysis of lncRNA-miRNA-mRNA expression pattern in heart tissue after total body radiation in a mouse model
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Journal Article
Analysis of lncRNA-miRNA-mRNA expression pattern in heart tissue after total body radiation in a mouse model
2021
Overview
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 48 h 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.
Publisher
BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
Subject
