Zhang Yingying, Zhang Yao, Li Xueqin, Zhang Mengying, Lv Kun
Laboratory Medicine, Yijishan Hospital, Wannan Medical College, Wuhu, Anhui 241001, P.R. China.
Department of Biochemistry, Wannan Medical College, Wuhu, Anhui 241001, P.R. China.
Int J Mol Med. 2017 Feb;39(2):373-379. doi: 10.3892/ijmm.2017.2852. Epub 2017 Jan 11.
Circular RNAs (circRNAs) are generated from diverse genomic locations and are a new player in the regulation of post-transcriptional gene expression. Recent studies have revealed that circRNAs play a crucial role in fine-tuning the level of microRNA (miRNA)-mediated regulation of gene expression by sequestering miRNAs. The interaction of circRNAs with disease-associated miRNAs suggests that circRNAs are important in the pathology of disease. However, the effects and roles of circRNAs in macrophage polarization have yet to be explored. In the present study, we performed a circRNA microarray to compare the circRNA expression profiles of bone marrow-derived macrophages (BMDMs) under two distinct polarizing conditions (M1 macrophages induced by interferon-γ and LPS stimulation, and M2 macrophages induced by interleukin-4 stimulation). Our results showed that a total of 189 circRNAs were differentially expressed between M1 and M2 macrophages. Differentially expressed circRNAs with a high fold-change were selected for validation by RT-qPCR: circRNA-003780, circRNA-010056, and circRNA-010231 were upregulated and circRNA-003424, circRNA-013630, circRNA-001489 and circRNA-018127 were downregulated (fold-change >4, P<0.05) in M1 compared to M2, which was found to correlate with the microarray data. Furthermore, the most differentially expressed circRNAs within all the comparisons were annotated in detail with circRNA/miRNA interaction information using miRNA target prediction software. In conclusion, the present study provides novel insight into the role of circRNAs in macrophage differentiation and polarization.
环状RNA（circRNAs）产生于不同的基因组位置，是转录后基因表达调控中的新成员。最近的研究表明，circRNAs通过隔离微小RNA（miRNA）在微调miRNA介导的基因表达调控水平中发挥关键作用。circRNAs与疾病相关miRNAs的相互作用表明circRNAs在疾病病理学中很重要。然而，circRNAs在巨噬细胞极化中的作用尚未得到探索。在本研究中，我们进行了circRNA微阵列分析，以比较在两种不同极化条件下（干扰素-γ和LPS刺激诱导的M1巨噬细胞，以及白细胞介素-4刺激诱导的M2巨噬细胞）骨髓来源巨噬细胞（BMDMs）的circRNA表达谱。我们的结果显示，M1和M2巨噬细胞之间共有189种circRNAs差异表达。选择具有高倍数变化的差异表达circRNAs通过RT-qPCR进行验证：与M2相比，circRNA-003780、circRNA-010056和circRNA-010231在M1中上调，而circRNA-003424、circRNA-013630、circRNA-001489和circRNA-018127在M1中下调（倍数变化>4，P<0.05），这与微阵列数据相关。此外，使用miRNA靶标预测软件，对所有比较中差异最显著的circRNAs进行了详细注释，并给出了circRNA/miRNA相互作用信息。总之，本研究为circRNAs在巨噬细胞分化和极化中的作用提供了新的见解。
