Protective effect of hepatocyte-enriched lncRNA-Mir122hg by promoting hepatocyte proliferation in acute liver injury.
Protective effect of hepatocyte-enriched lncRNA-Mir122hg by promoting hepatocyte proliferation in acute liver injury.
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富含肝细胞的lncRNA-Mir122hg通过促进肝细胞增殖对急性肝损伤的保护作用
DOI：
10.1038/s12276-022-00881-2
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发表时间：
2022-11
影响因子：
12.8
通讯作者：
Han, Tao
中科院分区：
文献类型：
--
作者：
Yu, Zhenjun;Li, Yuhan;Shao, Shuai;Guo, Beichen;Zhang, Mengxia;Zheng, Lina;Zhang, Kun;Zhou, Feng;Zhang, Li;Chen, Chiyi;Jiang, Wentao;Hong, Wei;Han, Tao
一些长链非编码RNA（lncRNA）在其基因序列中含有microRNA，也称为microRNA宿主基因衍生的lncRNA（lnc-MIRHGs），与miRNA一起发挥主导作用，或者两者协同或独立地执行生物学功能。然而，只有少数lnc-MIRHG已被确定。在这里，分析多个肝损伤数据集以筛选和鉴定靶lncRNA Mir 122 hg。Mir 122 hg主要富集在人-鼠同源的肝组织中。在CCl 4诱导的小鼠急性肝损伤和Dgal/LPS诱导的小鼠暴发性肝衰竭中，Mir 122 hg在早期急剧下调，而随后仅在CCl 4组肝脏恢复后出现显着增加。过表达和沉默实验证实，Mir 122 hg通过促进肝细胞增殖在体内和体外的急性损伤中发挥保护作用。与基因富集分析的结果一致，Mir 122 hg与C/EBPα的结合影响其转录抑制，促进下游趋化因子Cxcl 2、Cxcl 3和Cxcl 5的基因转录，并通过CXC/CXCR 2复合物激活AKT/GSK-3β/p27信号通路对肝细胞产生促增殖作用。本研究鉴定了一种在急性肝损伤中具有保护作用的新型lncRNA，并证明Mir 122 hg-C/EBPα的结合通过上调CXC趋化因子和激活AKT信号传导促进肝细胞增殖。
Some long noncoding RNAs (lncRNAs), which harbor microRNAs in their gene sequence and are also known as microRNA host gene derived lncRNAs (lnc-MIRHGs), play a dominant role alongside miRNAs, or both perform biological functions synergistically or independently. However, only a small number of lnc-MIRHGs have been identified. Here, multiple liver injury datasets were analyzed to screen and identify the target lncRNA Mir122hg. Mir122hg was mainly enriched in liver tissues with human-mouse homology. In both CCl4-induced acute liver injury and Dgal/LPS-induced fulminant liver failure in mice, Mir122hg was sharply downregulated at the early stage, while a subsequent significant increase was only found in the CCl4 group with liver recovery. Overexpression and silencing assays confirmed that Mir122hg played a protective role in acute injury by promoting hepatocyte proliferation in vivo and in vitro. Consistent with the results of gene enrichment analysis, Mir122hg binding to C/EBPα affected its transcriptional repression, promoted gene transcription of downstream chemokines, Cxcl2, Cxcl3, and Cxcl5, and exerted pro-proliferative effects on hepatocytes through activation of the AKT/GSK-3β/p27 signaling pathway by CXC/CXCR2 complexes. This study identifies a novel lncRNA with protective effects in acute liver injury and demonstrates that the binding of Mir122hg-C/EBPα promotes hepatocyte proliferation via upregulation of CXC chemokine and activation of AKT signaling.
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影响因子：
16.8
作者：
Dhir, Ashish;Dhir, Somdutta;Proudfoot, Nick J.;Jopling, Catherine L.
通讯作者：
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DOI：
10.1016/j.tig.2017.11.005
发表时间：
2018-03
期刊：
Trends in genetics : TIG
影响因子：
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DOI：
10.1152/ajpgi.00350.2018
发表时间：
2019-03-01
影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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影响因子：
3.3
作者：
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通讯作者：
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