Compared Analysis of LncRNA Expression Profiling in pdk1 Gene Knockout Mice at Two Time Points
Compared Analysis of LncRNA Expression Profiling in pdk1 Gene Knockout Mice at Two Time Points
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DOI：
10.1159/000356586
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发表时间：
2013-01-01
影响因子：
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通讯作者：
Qian, Lingmei
中科院分区：
文献类型：
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作者：
Liu, Hailang;Song, Guixian;Qian, Lingmei
背景/目的：研究表明，长链非编码RNA（longnoncodingRNA，lncRNA）与癌症、HELLP、短指综合征等多种人类疾病的发生、发展有关。然而，LncRNA在心力衰竭中的研究尚未报道。在这里，我们研究了心肌特异性敲除pdk 1基因（KO）心力衰竭小鼠模型的心脏lncRNA表达谱。研究方法：在出生后（P）第8天（P8）和第40天（P40）从PDK 1 KO和WT小鼠获得心脏样品，并使用Arraystar小鼠lncRNA微阵列通过测序和筛选来分析lncRNA表达谱。这些lncRNA的定量实时PCR分析证实了一些基因的身份。结果如下：KO组和对照组的比较显示在P8时2，024个lncRNA的表达水平的倍数变化>1.5，而在P40时检测到4，095个lncRNA的表达水平的倍数变化>2。通过RT-PCR验证了19种lncRNA。生物信息学和通路分析表明，mkk 7是一种有义重叠的lncRNA，可能通过MAPK信号通路参与心力衰竭的病理过程。结论：这些数据揭示了心肌特异性缺失pdk 1基因的小鼠中差异表达的lncRNA，这可能为PDK 1基因敲除小鼠心力衰竭机制提供新的见解。版权所有（C）2013 S. Karger AG，巴塞尔
Background/Aims: Previous studies have indicated that long non-coding RNAs (lncRNA) are related to the occurrence and development of many human diseases, such as cancer and the HELLP and the brachydactyly syndromes. However, studies of LncRNA in heart failure have not yet been reported. Here, we investigated cardiac lncRNA expression profiles in the myocardial-specific knockout pdk1 gene (KO) mouse model of heart failure. Methods: Cardiac samples were obtained from PDK1 KO and WT mice on postnatal (P) day 8 (P8) and day 40 (P40), and lncRNA expression profiles were analyzed by sequencing and screening using the Arraystar mouse lncRNA microarray. Quantitative real-time PCR analysis of these lncRNAs confirmed the identity of some genes. Results: Comparisons of the KO and control groups showed fold changes of >1.5 in the expression levels of 2,024 lncRNAs at P8, while fold changes of >2 in the expression levels of 4,095 lncRNAs were detected at P40. Nineteen lncRNAs were validated by RT-PCR. Bioinformatic and pathway analyses indicated that mkk7, a sense overlap lncRNA, may be involved in the pathological processes of heart failure through the MAPK signaling pathway. Conclusion: These data reveal differentially expressed lncRNA in mice with a myocardial-specific deletion of the pdk1 gene, which may provide new insights into the mechanism of heart failure in PDK1 knockout mice. Copyright (C) 2013 S. Karger AG, Basel