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转录组分析揭示了 lnc-5423.6/IGFBP5 轴在小鼠胸腺早期退化中的潜在调控机制。

Transcriptome analysis reveals a potential regulatory mechanism of the lnc-5423.6/IGFBP5 axis in the early stages of mouse thymic involution.

机构信息

College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China.

College of Animal Science & Technology, Guangdong Province Key Laboratory of Waterfowl Healthy Breeding, Zhongkai University of Agriculture and Engineering, Guangzhou 510225, China.

出版信息

Acta Biochim Biophys Sin (Shanghai). 2023 Apr 19;55(4):548-560. doi: 10.3724/abbs.2023042.

Abstract

Age-related thymic involution is one of the significant reasons for induced immunity decline. Recent evidence has indicated that lncRNAs are widely involved in regulating organ development. However, the lncRNA expression profiles in mouse thymic involution have not been reported. In this study, we collect mouse thymus at the ages of 1 month, 3 months, and 6 months for sequencing to observe the lncRNA and gene expression profiles in the early stages of thymic involution. Through bioinformatics analysis, a triple regulatory network of lncRNA-miRNA-mRNA that contains 29 lncRNAs, 145 miRNAs and 12 mRNAs that may be related to thymic involution is identified. Among them, IGFBP5 can reduce the viability, inhibit proliferation and promote apoptosis of mouse medullary thymic epithelial cell line 1 (MTEC1) cells through the p53 signaling pathway. In addition, miR-193b-3p can alleviate MTEC1 cell apoptosis by targeting . Notably, lnc-5423.6 can act as a molecular sponge of miR-193b-3p to regulate the expression of IGFBP5. In summary, lnc-5423.6 enhances the expression of IGFBP5 by adsorption of miR-193b-3p, thereby promoting MTEC1 cell apoptosis.

摘要

年龄相关性胸腺萎缩是诱导免疫功能下降的重要原因之一。最近的证据表明,lncRNAs 广泛参与调节器官发育。然而,lncRNA 在小鼠胸腺萎缩中的表达谱尚未报道。在这项研究中,我们收集了 1 个月、3 个月和 6 个月大的小鼠胸腺进行测序,以观察胸腺萎缩早期的 lncRNA 和基因表达谱。通过生物信息学分析,确定了一个包含 29 个 lncRNA、145 个 miRNA 和 12 个 mRNA 的 lncRNA-miRNA-mRNA 三重调控网络,这些 lncRNA、miRNA 和 mRNA 可能与胸腺萎缩有关。其中,IGFBP5 可通过 p53 信号通路降低小鼠髓质胸腺上皮细胞系 1(MTEC1)细胞的活力、抑制增殖并促进其凋亡。此外,miR-193b-3p 可通过靶向 来减轻 MTEC1 细胞凋亡。值得注意的是,lnc-5423.6 可以作为 miR-193b-3p 的分子海绵来调节 IGFBP5 的表达。总之,lnc-5423.6 通过吸附 miR-193b-3p 增强 IGFBP5 的表达,从而促进 MTEC1 细胞凋亡。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/98de/10195152/81ddc9e145ce/abbs-2022-356-t1.jpg

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