Key Laboratory of Non-coding RNA Transformation Research of Anhui Higher Education Institutes, Wannan Medical College, Wuhu, PR China.
Central Laboratory of Yijishan Hospital, Wannan Medical College, Wuhu, PR China.
FASEB J. 2020 Apr;34(4):5077-5091. doi: 10.1096/fj.201902379R. Epub 2020 Feb 13.
Long non-coding RNAs (lncRNAs) play key roles in various biological processes. However, the roles of lncRNAs in macrophage polarization remain largely unexplored. In this study, thousands of lncRNAs were identified that are differentially expressed in distinct polarized bone marrow-derived macrophages. Among them, Dnmt3aos (DNA methyltransferase 3A, opposite strand), as a known lncRNA, locates on the antisense strand of Dnmt3a. Functional experiments further confirmed that Dnmt3aos were highly expressed in M(IL-4) macrophages and participated in the regulation of Dnmt3a expression, and played a key role in macrophage polarization. The DNA methylation profiles between the Dnmt3aos knockdown group and the control group in M(IL-4) macrophages were determined by MeDIP-seq technique for the first time, and the Dnmt3aos-Dnmt3a axis-mediated DNA methylation modification-regulated macrophage polarization- related gene IFN-γ was identified. Our study will help to enrich our knowledge of the mechanism of macrophage polarization.
长非编码 RNA（lncRNA）在各种生物过程中发挥着关键作用。然而，lncRNA 在巨噬细胞极化中的作用在很大程度上仍未被探索。在这项研究中，鉴定了数千种在不同极化的骨髓来源巨噬细胞中差异表达的 lncRNA。其中，Dnmt3aos（DNA 甲基转移酶 3A，反义链）作为一种已知的 lncRNA，位于 Dnmt3a 的反义链上。功能实验进一步证实，Dnmt3aos 在 M（IL-4）巨噬细胞中高表达，并参与 Dnmt3a 表达的调控，在巨噬细胞极化中发挥关键作用。首次通过 MeDIP-seq 技术确定了 Dnmt3aos 敲低组和对照组在 M（IL-4）巨噬细胞中的 DNA 甲基化谱，鉴定了 Dnmt3aos-Dnmt3a 轴介导的 DNA 甲基化修饰调控巨噬细胞极化相关基因 IFN-γ。我们的研究将有助于丰富我们对巨噬细胞极化机制的认识。
