HIV-1 Nef-induced lncRNA AK006025 regulates CXCL9/10/11 cluster gene expression in astrocytes through interaction with CBP/P300.
HIV-1 Nef-induced lncRNA AK006025 regulates CXCL9/10/11 cluster gene expression in astrocytes through interaction with CBP/P300.
复制标题
HIV-1 Nef 诱导的 lncRNA AK006025 通过与 CBP/P300 相互作用调节星形胶质细胞中的 CXCL9/10/11 簇基因表达
DOI：
10.1186/s12974-018-1343-x
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发表时间：
2018-10-31
影响因子：
9.3
通讯作者：
Tang R
中科院分区：
文献类型：
--
作者：
Zhou F;Liu X;Zuo D;Xue M;Gao L;Yang Y;Wang J;Niu L;Cao Q;Li X;Hua H;Zhang B;Hu M;Gao D;Zheng K;Izumiya Y;Tang R
研究背景HIV相关神经认知障碍（HAND）是一种以持续性神经炎症和神经元损伤为特征的神经退行性疾病。HIV-1及其编码蛋白激活星形胶质细胞产生的促炎因子和神经毒素，包括负性因子（Nef），参与了HAND的发病机制。本研究旨在寻找潜在的lncRNAs，调节星形胶质细胞的功能和炎症processes.MethodsWe进行基因芯片分析lncRNAs从原代小鼠星形胶质细胞Nef蛋白处理。通过实时PCR分析验证前十个lncRNA。应用基因本体论（GO）和KEGG通路分析方法探讨lncRNA的潜在功能。结果Nef蛋白处理6 h和12 h后，原代星形胶质细胞共上调lncRNA 638条，下调lncRNA 372条。GO和KEGG通路分析显示，差异表达最高的mRNA的生物学功能与炎性细胞因子和趋化因子有关。在用Nef蛋白处理的星形胶质细胞中，敲低lncRNA AK 006025而不是AK 138360显著抑制CXCL 9、CXCL 10（IP-10）和CXCL 11表达。机制研究表明，与CBP/P300相关的AK 006025富集于CXCL 9、CXCL 10和CXCL 11基因的启动子区。
BackgroundHIV-associated neurocognitive disorder (HAND) is a neurodegenerative disease associated with persistent neuroinflammation and subsequent neuron damage. Pro-inflammatory factors and neurotoxins from activated astrocytes by HIV-1 itself and its encoded proteins, including the negative factor (Nef), are involved in the pathogenesis of HAND. This study was designed to find potential lncRNAs that regulate astrocyte functions and inflammation process.MethodsWe performed microarray analysis of lncRNAs from primary mouse astrocytes treated with Nef protein. Top ten lncRNAs were validated through real-time PCR analysis. Gene ontology (GO) and KEGG pathway analysis were applied to explore the potential functions of lncRNAs. RIP and ChIP assays were performed to demonstrate the mechanism of lncRNA regulating gene expression.ResultsThere were 638 co-upregulated lncRNAs and 372 co-downregulated lncRNAs in primary astrocytes treated with Nef protein for both 6 h and 12 h. GO and KEGG pathway analysis showed that the biological functions of top differential-expressed mRNAs were associated with inflammatory cytokines and chemokine. Knockdown of lncRNA AK006025, not AK138360, inhibited significantly CXCL9, CXCL10 (IP-10), and CXCL11 expression in astrocytes treated with Nef protein. Mechanism study showed that AK006025 associated with CBP/P300 was enriched in the promoter of CXCL9, CXCL10, and CXCL11 genes.ConclusionsOur findings uncovered the expression profiles of lncRNAs and mRNAs in vitro, which might help to understand the pathways that regulate astrocyte activation during the process of HAND.
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影响因子：
32.4
作者：
Kang Z;Altuntas CZ;Gulen MF;Liu C;Giltiay N;Qin H;Liu L;Qian W;Ransohoff RM;Bergmann C;Stohlman S;Tuohy VK;Li X
通讯作者：
Li X
影响因子：
6.1
作者：
Chompre G;Cruz E;Maldonado L;Rivera-Amill V;Porter JT;Noel RJ Jr
通讯作者：
Noel RJ Jr
影响因子：
64.5
作者：
KESTLER, HW;RINGLER, DJ;DESROSIERS, RC
通讯作者：
DESROSIERS, RC
影响因子：
64.5
作者：
Bose DA;Donahue G;Reinberg D;Shiekhattar R;Bonasio R;Berger SL
通讯作者：
Berger SL
影响因子：
6.1
作者：
Gaskill PJ;Miller DR;Gamble-George J;Yano H;Khoshbouei H
通讯作者：
Khoshbouei H