Circular RNA Profiling and Bioinformatic Modeling Identify Its Regulatory Role in Hepatic Steatosis.
Circular RNA Profiling and Bioinformatic Modeling Identify Its Regulatory Role in Hepatic Steatosis.
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环状 RNA 分析和生物信息学模型确定其在肝脂肪变性中的调节作用
DOI：
10.1155/2017/5936171
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发表时间：
2017
影响因子：
--
通讯作者：
Fan JG
中科院分区：
文献类型：
--
作者：
Guo XY;He CX;Wang YQ;Sun C;Li GM;Su Q;Pan Q;Fan JG
环状RNA（circRNA）具有广泛的生理和病理活性。为了揭示它们在肝脂肪变性中的作用，我们研究了circRNA在由高脂肪刺激诱导的基于HepG 2的肝脂肪变性中的表达谱。分别使用QPCR和使用主成分分析、层次聚类、靶标预测、基因本体（GO）和途径注释的功能分析对差异表达的circRNA进行验证。生物信息学整合建立了circRNA-miRNA-mRNA的调控网络，以明确circRNA的代谢作用机制。在这里，我们报道了肝脂肪变性与总共357个circRNA相关。转录相关基因GO：0006355、GO：004589、GO：0045944、GO：0045892和GO：0000122的富集显示了它们在转录调控中的特异性作用。脂蛋白1（Lipin 1，LPIN 1）被认为介导circRNA对代谢途径的转录调控作用。circRNA-miRNA-mRNA网络进一步鉴定了circRNA_021412/miR-1972/LPIN 1的信号级联，其特征在于基于circRNA_021412和miR-1972的LPIN 1抑制水平降低。LPIN 1诱导的长链酰基辅酶A合成酶（ACSL）表达下调最终导致脂肪肝。这些发现确定circRNA是肝脂肪变性的重要调节因子。代谢途径的转录依赖性调节可能是其作用的基础，部分通过circRNA_021412/miR-1972/LPIN 1信号传导。
Circular RNAs (circRNAs) exhibit a wide range of physiological and pathological activities. To uncover their role in hepatic steatosis, we investigated the expression profile of circRNAs in HepG2-based hepatic steatosis induced by high-fat stimulation. Differentially expressed circRNAs were subjected to validation using QPCR and functional analyses using principal component analysis, hierarchical clustering, target prediction, gene ontology (GO), and pathway annotation, respectively. Bioinformatic integration established the circRNA-miRNA-mRNA regulatory network so as to identify the mechanisms underlying circRNAs' metabolic effect. Here we reported that hepatic steatosis was associated with a total of 357 circRNAs. Enrichment of transcription-related GOs, especially GO: 0006355, GO: 004589, GO: 0045944, GO: 0045892, and GO: 0000122, demonstrated their specific actions in transcriptional regulation. Lipin 1 (LPIN1) was recognized to mediate the transcriptional regulatory effect of circRNAs on metabolic pathways. circRNA-miRNA-mRNA network further identified the signaling cascade of circRNA_021412/miR-1972/LPIN1, which was characterized by decreased level of circRNA_021412 and miR-1972-based inhibition of LPIN1. LPIN1-induced downregulation of long chain acyl-CoA synthetases (ACSLs) expression finally resulted in the hepatosteatosis. These findings identify circRNAs to be important regulators of hepatic steatosis. Transcription-dependent modulation of metabolic pathways may underlie their effects, partially by the circRNA_021412/miR-1972/LPIN1 signaling.