Analysis of lncRNA-miRNA-mRNA expression pattern in heart tissue after total body radiation in a mouse model

作者：Molykutty J. Aryankalayil, Shannon Martello, Michelle A. Bylicky, Sunita Chopra, Jared M. May, Aman Shankardass, Laurel MacMillan, Landy Sun, Jaleal Sanjak, Claire Vanpouille‐Box, Iris Eke, C. Norman Coleman · 发表于：Journal of Translational Medicine · 年份：2021 · DOI：10.1186/s12967-021-02998-w · 被引用次数：40 · 研究领域：Effects of Radiation Exposure、Chemotherapy-induced cardiotoxicity and mitigation、MicroRNA in disease regulation

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. Ad...