CircIBTK inhibits DNA demethylation and activation of AKT signaling pathway via miR-29b in peripheral blood mononuclear cells in systemic lupus erythematosus.
CircIBTK inhibits DNA demethylation and activation of AKT signaling pathway via miR-29b in peripheral blood mononuclear cells in systemic lupus erythematosus.
复制标题
CircIBTK 通过 miR-29b 抑制系统性红斑狼疮外周血单个核细胞 DNA 去甲基化和 AKT 信号通路激活
DOI：
10.1186/s13075-018-1618-8
复制
发表时间：
2018-06-08
影响因子：
4.9
通讯作者：
Shi W
中科院分区：
文献类型：
--
作者：
Wang X;Zhang C;Wu Z;Chen Y;Shi W
系统性红斑狼疮（SLE）是一种慢性且无法治愈的自身免疫性疾病，涉及淋巴细胞功能障碍。环状RNA（circRNA）是具有共价闭环结构的非编码RNA（ncRNA），在人类多种疾病中异常表达可能参与发病机制，而在SLE中需要进一步研究。在本研究中，我们旨在寻找SLE中异常表达的circRNA并探讨circRNA在SLE中的功能。采用circRNA测序发现异常表达的circRNA，并采用qRT-PCR检测表达情况。采用相关分析来分析 circIBTK 或 miR-29b 与 SLE 患者临床病理变量之间的相关性。使用细胞培养、核质分离、qRT-PCR、转染、荧光素酶报告基因测定、蛋白质印迹分析、DNA提取和全局甲基化分析来解释circIBTK和miR-29b在SLE进展中的功能。采用SPSS 18.0软件进行统计。我们发现 circIBTK 的表达在 SLE 中下调，并与 SLE 患者的系统性红斑狼疮疾病活动指数 (SLEDAI) 评分、抗双链 (ds)DNA 和补体 C3 水平相关。然后，miR-29b 表达在 SLE 中上调，并与 SLE 患者的 SLEDAI 评分、抗 dsDNA 和补体 C3 水平相关。机制研究表明，miR-29b 可以诱导 DNA 去甲基化并激活 AKT 信号通路，而 circIBTK 可能通过与 SLE 中的 miR-29b 结合来逆转 miR-29b 诱导的 DNA 去甲基化和 AKT 信号通路激活。 CircIBTK 在 SLE 中下调，可能通过与 SLE 中的 miR-29b 结合来调节 DNA 去甲基化和 AKT 信号通路。 CircIBTK 和 miR-29 也可以作为 SLE 的生物标志物和治疗靶点。本文的在线版本 (10.1186/s13075-018-1618-8) 包含补充材料，可供授权用户使用。
Systemic lupus erythematosus (SLE) is a chronic and incurable autoimmune disease involving the dysfunction of lymphocytes. Circular RNAs (circRNAs) are noncoding RNAs (ncRNAs) with a covalently closed loop structure, with abnormal expression in various human diseases may participate in the pathogenesis, while further study is needed in SLE. In this study, we aimed to find the circRNAs abnormally expressed in SLE and explore the function of circRNAs in SLE. CircRNA sequencing was used to find the abnormally expressed circRNA and qRT-PCR was used to detect the expression. Correlation analysis was used to analyze the correlation between circIBTK or miR-29b and clinicopathological variables in patients with SLE. Cell culture, nuclear-cytoplasmic fractionation, qRT-PCR, transfection, luciferase reporter assay, western blot analysis, DNA extraction and global methylation analysis were used to explain the function of circIBTK and miR-29b in the progression of SLE. SPSS 18.0 software was used to perform statistics. We found that the expression of circIBTK was downregulated in SLE and correlated with Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score, anti-double-stranded (ds)DNA and complement C3 level in patients with SLE. Then miR-29b expression was upregulated in SLE and correlated with SLEDAI score, anti-dsDNA and complement C3 level in patients with SLE. Mechanistic investigations indicated that miR-29b could induce DNA demethylation and activate the AKT signaling pathway and circIBTK might reverse the DNA demethylation and activation of the AKT signaling pathway induced by miR-29b via binding to miR-29b in SLE. CircIBTK was downregulated in SLE and might regulate DNA demethylation and the AKT signaling pathway via binding to miR-29b in SLE. CircIBTK and miR-29 could also act as biomarkers and therapeutic targets for SLE. The online version of this article (10.1186/s13075-018-1618-8) contains supplementary material, which is available to authorized users.
登录
查看更多内容
蛋白激酶B控制着指导细胞毒性T细胞命运但对于T细胞代谢的转录程序。
影响因子：
32.4
作者：
Macintyre AN;Finlay D;Preston G;Sinclair LV;Waugh CM;Tamas P;Feijoo C;Okkenhaug K;Cantrell DA
通讯作者：
Cantrell DA
DOI：
10.1038/nri2888
发表时间：
2011-02
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
影响因子：
--
作者：
Li F;Zhang L;Li W;Deng J;Zheng J;An M;Lu J;Zhou Y
通讯作者：
Zhou Y
影响因子：
82.9
作者：
Barber, DF;Bartolomé, A;Carrera, AC
通讯作者：
Carrera, AC
影响因子：
--
作者：
Mina-Osorio, Paola;LaStant, Jacob;Xu, Daigen
通讯作者：
Xu, Daigen