Analysis of lncRNA-miRNA-mRNA expression pattern in heart tissue after total body radiation in a mouse model.
Analysis of lncRNA-miRNA-mRNA expression pattern in heart tissue after total body radiation in a mouse model.
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DOI：
10.1186/s12967-021-02998-w
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发表时间：
2021-08-07
影响因子：
7.4
通讯作者：
Coleman CN
中科院分区：
文献类型：
--
作者：
Aryankalayil MJ;Martello S;Bylicky MA;Chopra S;May JM;Shankardass A;MacMillan L;Sun L;Sanjak J;Vanpouille-Box C;Eke I;Coleman CN
放射治疗是有效的胸部癌症治疗不可或缺的一部分，但其应用受到心脏等关键器官敏感性的限制。随着患者寿命的延长，急性辐射损伤及其对正常心脏细胞的慢性效应与放射治疗高度相关。目前正在研究辐射照射后正常组织损伤的生物标志物，无论是意外照射还是治疗照射，作为急性效应和延迟效应的指标。最近的研究强调了RNA，包括信使RNA（mRNA）、微小RNA（miRNA）和长链非编码RNA（lncRNA）作为评估辐射损伤的生物标志物的潜在重要性。了解mRNA和非编码RNA表达的变化将阐明辐射后生物途径的变化。为了鉴定mRNA、lncRNA和miRNA的显著表达变化，我们在用1、2、4、8和12戈瑞（戈伊）全身照射后48小时对小鼠心脏组织进行全转录组微阵列分析。我们还通过RT-qPCR验证了特异性lncRNA的变化。使用独创性途径分析（IPA）来识别与基因表达变化相关的途径。在所有剂量的辐射中，我们观察到lncRNA和mRNA的持续增加。Alas 2、Aplnr和Cxc 3r 1是所有剂量下最显著下调的mRNA。在显著上调的mRNA中，有细胞周期阻滞生物标志物Gdf 15、Cdkn 1a和Ckap 2。此外，IPA鉴定了与衰老、凋亡、血红蛋白合成、炎症和代谢相关的基因表达的显著变化。LncRNA Abhd 11 os、Pvt 1、Trp 53 cor 1和Dino的表达随着辐射剂量的增加而增加。我们没有观察到任何miRNA在所有剂量下持续上调或下调，但miR-149- 3 p、miR-6538、miR-8101、miR-7118- 5 p、miR-211- 3 p和miR-3960在12戈伊后显著上调。辐射诱导的RNA表达变化可能是正常组织毒性的预测，并可能表明放射对策发展和改进放射治疗计划的靶向途径。在线版本包含补充材料，可通过10.1186/s12967-021-02998-w获得。
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. 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. 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. 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. The online version contains supplementary material available at 10.1186/s12967-021-02998-w.
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影响因子：
2
作者：
Beer L;Nemec L;Wagner T;Ristl R;Altenburger LM;Ankersmit HJ;Mildner M
通讯作者：
Mildner M
影响因子：
2.2
作者：
Farese AM;Cohen MV;Katz BP;Smith CP;Jackson W 3rd;Cohen DM;MacVittie TJ
通讯作者：
MacVittie TJ
影响因子：
2.6
作者：
Dogan, Aysegul
通讯作者：
Dogan, Aysegul
DOI：
10.1016/j.ijrobp.2012.02.029
发表时间：
2012-09-01
影响因子：
7
作者：
Feng, Mary;Normolle, Daniel;Ten Haken, Randall K.
通讯作者：
Ten Haken, Randall K.
DOI：
10.1158/1078-0432.ccr-20-0572
发表时间：
2020-11-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Coleman CN;Eke I;Makinde AY;Chopra S;Demaria S;Formenti SC;Martello S;Bylicky M;Mitchell JB;Aryankalayil MJ
通讯作者：
Aryankalayil MJ