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自噬过程中长链非编码 RNA 表达谱及 Malat1 在巨噬细胞中的功能。

LncRNA expression profile during autophagy and Malat1 function in macrophages.

机构信息

Ningxia Key Laboratory of Clinical and Pathogenic Microbiology, General Hospital of Ningxia Medical University, Yinchuan, China.

Department of Medical Genetic and Cell Biology, College of Basic Medicine, Ningxia Medical University, Yinchuan, China.

出版信息

PLoS One. 2019 Aug 19;14(8):e0221104. doi: 10.1371/journal.pone.0221104. eCollection 2019.

Abstract

Long noncoding RNAs (lncRNAs) are a class of functional non-coding transcripts that are longer than 200 nt and regulate gene expression via diverse mechanisms in eukaryotes. In fact, they have emerged as critical epigenetic and transcriptional regulators of autophagy in mammals in response to various stressors. Autophagy not only plays a crucial role in maintaining cellular homeostasis, but it is also essential to immunity, targets intracellular pathogens for degradation, modulates inflammation, and participates in adaptive immune responses. However, the expression profile of lncRNA and its role in regulating autophagy in macrophages have been poorly defined. Here, we used transcriptomic and bioinformatics to analysis LncRNA expression profile during autophagy and functional studies to evaluate the function of the metastasis-associated lung adenocarcinoma transcript-1 (Malat1) lncRNA in macrophages. A total of 1112 putative lncRNAs (240 novel lncRNAs) were identified, including 831 large intergenic, 129 intronic, and 152 anti-sense lncRNA, of which 59 differentially expressed transcripts exhibited a greater than 1.5-fold change under different conditions. The interaction of Malat1 lncRNA with microRNA (mir)-23-3p and lysosomal-associated membrane protein 1 (Lamp1) was found, Malat1 releases inhibition of Lamp1 expression in macrophages through competitive adsorption of mir-23-3p. The results of this study provide a better understanding of lncRNA function in macrophages and a basis for further investigation into the roles and mechanisms of ncRNA in immunology, particularly the functions of Malat1 and mir-23-3p in the pathogenesis of macrophages.

摘要

长链非编码 RNA(lncRNA)是一类功能非编码转录本,其长度大于 200nt,并通过真核生物中的多种机制调节基因表达。事实上,它们已成为哺乳动物中应对各种应激原时自噬的关键表观遗传和转录调节因子。自噬不仅在维持细胞内稳态中起着至关重要的作用,而且对于免疫也是必不可少的,它可以靶向细胞内病原体进行降解,调节炎症,并参与适应性免疫反应。然而,lncRNA 的表达谱及其在调节巨噬细胞自噬中的作用仍未得到充分定义。在这里,我们使用转录组学和生物信息学分析自噬过程中的 lncRNA 表达谱,并进行功能研究,以评估转移相关肺腺癌转录本-1(Malat1)lncRNA 在巨噬细胞中的功能。总共鉴定出 1112 个假定的 lncRNA(240 个新的 lncRNA),包括 831 个大基因间、129 个内含子和 152 个反义 lncRNA,其中 59 个差异表达转录本在不同条件下表现出大于 1.5 倍的变化。发现 Malat1 lncRNA 与 microRNA(mir)-23-3p 和溶酶体相关膜蛋白 1(Lamp1)相互作用,Malat1 通过竞争性吸附 mir-23-3p 释放对巨噬细胞中 Lamp1 表达的抑制作用。本研究结果提供了对巨噬细胞中 lncRNA 功能的更好理解,并为进一步研究 ncRNA 在免疫学中的作用和机制,特别是 Malat1 和 mir-23-3p 在巨噬细胞发病机制中的功能提供了基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8eb6/6699732/f421a07178a8/pone.0221104.g001.jpg

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