Burkholderia pseudomallei survival in lung epithelial cells benefits from miRNA-mediated suppression of ATG10
Burkholderia pseudomallei survival in lung epithelial cells benefits from miRNA-mediated suppression of ATG10
复制标题
鼻疽伯克霍尔德氏菌在肺上皮细胞中的存活受益于 miRNA 介导的 ATG10 抑制
DOI：
10.1080/15548627.2015.1058474
复制
发表时间：
2015-08-01
期刊：
影响因子：
13.3
通讯作者：
Mao, Xu-hu
中科院分区：
文献类型：
--
作者：
Li, Qian;Fang, Yao;Mao, Xu-hu
鼻疽伯克霍尔德氏菌是类鼻疽的病原体，类鼻疽是一种死亡率很高的疾病，在世界热带地区流行。最近的一项研究表明，类鼻疽杆菌能够在哺乳动物细胞内存活，因为它能够主动逃避细胞自噬。然而，其根本机制仍不清楚。在本研究中，基于微阵列筛选，我们发现 A549 人肺上皮细胞中 ATG10 在类鼻疽杆菌感染后下调。 ATG10 的强制表达通过增强自噬过程加速了细胞内类鼻疽杆菌的消除。此外，通过微阵列筛选，发现 MIR4458、MIR4667-5p 和 MIR4668-5p 在对类鼻疽杆菌感染的反应中上调。这 3 个新的 miRNA，MIR4458、MIR4667-5p 和 MIR4668-5p，以不同的时程和空间方式靶向 ATG10 的 3'-非翻译区。这些 miRNA 的上调可降低 ATG10 的水平并抑制自噬，从而提高细胞内类鼻疽伯克霍尔德氏菌的存活率。此外，这些 miRNA 的增加与 A549 细胞中响应假鼻疽杆菌感染而降低的启动子甲基化状态相关。我们的结果揭示了 3 个新的 miRNA 通过靶向 ATG10 来调节自噬介导的类鼻疽杆菌的消除，并为临床治疗提供了潜在的靶点。
Burkholderia pseudomallei is the causative agent of melioidosis, a disease with high mortality, which is prevalent in tropical regions of the world. A recent study shows that B. pseudomallei can survive inside mammalian cells because of its ability to actively evade cell autophagy. However, the underlying mechanisms remain unclear. In the present study, based on microarray screening, we found that ATG10 was downregulated following B. pseudomallei infection in A549 human lung epithelial cells. Forced expression of ATG10 accelerated the elimination of intracellular B. pseudomallei by enhancing the process of autophagy. Moreover, MIR4458, MIR4667-5p, and MIR4668-5p were found, by microarray screening, to be upregulated in response to B. pseudomallei infection. These 3 novel miRNAs, MIR4458, MIR4667-5p, and MIR4668-5p, targeted to the 3′-untranslated region of ATG10 in different time-course and spatial manners. Upregulation of these miRNAs reduced the level of ATG10 and inhibited autophagy, leading to increasing survival rate of intracellular B. pseudomallei. Furthermore, the increase of these miRNAs was correlated with the reduced promoter methylation status in A549 cells in response to B. pseudomallei infection. Our results reveal that 3 novel miRNAs regulate autophagy-mediated elimination of B. pseudomallei by targeting ATG10, and provide potential targets for clinical treatment.