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构建并综合分析长链非编码 RNA-信使 RNA 相互作用网络,以揭示潜在的肝性脑病发展的长链非编码 RNA。

Construction and comprehensive analysis of a lncRNA-mRNA interactive network to reveal a potential lncRNA for hepatic encephalopathy development.

机构信息

Department of General Surgery, Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University, 639 Zhi Zao Ju Road, Huangpu District, Shanghai, 200011, China.

Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology, Wuhan, China.

出版信息

Hum Cell. 2022 Jul;35(4):1060-1070. doi: 10.1007/s13577-022-00714-4. Epub 2022 May 18.

DOI:10.1007/s13577-022-00714-4
PMID:35583799
Abstract

Little is known about the role of lncRNA-mRNA regulatory relationships in hepatic encephalopathy (HE). Here, we aimed to construct the potential lncRNA and mRNA interactive network in forecasting HE development in patients with liver cirrhosis using different bioinformatic analysis method. Through analyses, we found that AL137857.1 had the most connections with other mRNAs and was deemed as a hub lncRNA. It was obviously upregulated in HE patients, which was also validated by another independent dataset. GO and KEGG analyses suggested that AL137857.1 was involved in microglial cell activation, phagocytosis, cytokine biosynthetic process, interleukin-6 production and tumor necrosis factor production. In vitro experiments suggested LPS could stimulate microglia to generate AL137857.1. In addition, we found that inhibition of AL137857.1 suppressed the expression of a series of inflammatory cytokines, including IL-1, IL-6, TNF-α, Cox2 and iNOS. Conversely, AL137857.1 over-expression induced a marked increase in these factors. Finally, AL137857.1 was demonstrated to be highly associated with the ability of microglial phagocytosis. Taken together, we have constructed a lncRNA-mRNA regulatory network associated with HE and explored the biological significance of mRNAs in the network, then discovered a novel lncRNA AL137857.1 in HE that might act as a potential regulator of the downstream inflammatory cytokines.

摘要

lncRNA-mRNA 调控关系在肝性脑病(HE)中的作用知之甚少。在这里,我们旨在使用不同的生物信息学分析方法构建预测肝硬化患者 HE 发展的潜在 lncRNA 和 mRNA 相互作用网络。通过分析,我们发现 AL137857.1 与其他 mRNAs 的连接最多,被认为是一个枢纽 lncRNA。它在 HE 患者中明显上调,这也被另一个独立数据集所验证。GO 和 KEGG 分析表明,AL137857.1 参与小胶质细胞激活、吞噬作用、细胞因子生物合成过程、白细胞介素-6 产生和肿瘤坏死因子产生。体外实验表明 LPS 可以刺激小胶质细胞产生 AL137857.1。此外,我们发现抑制 AL137857.1 抑制了一系列炎症细胞因子的表达,包括 IL-1、IL-6、TNF-α、Cox2 和 iNOS。相反,AL137857.1 的过表达诱导这些因子显著增加。最后,AL137857.1 被证明与小胶质细胞吞噬能力高度相关。总之,我们构建了与 HE 相关的 lncRNA-mRNA 调控网络,并探讨了网络中 mRNAs 的生物学意义,然后发现了一种在 HE 中可能作为下游炎症细胞因子潜在调节剂的新型 lncRNA AL137857.1。

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