microRNA-20a Inhibits Autophagic Process by Targeting ATG7 and ATG16L1 and Favors Mycobacterial Survival in Macrophage Cells.
microRNA-20a Inhibits Autophagic Process by Targeting ATG7 and ATG16L1 and Favors Mycobacterial Survival in Macrophage Cells.
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microRNA-20a 通过靶向 ATG7 和 ATG16L1 抑制自噬过程并有利于巨噬细胞中分枝杆菌的存活
DOI：
10.3389/fcimb.2016.00134
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发表时间：
2016
影响因子：
5.7
通讯作者：
Xu G
中科院分区：
文献类型：
--
作者：
Guo L;Zhao J;Qu Y;Yin R;Gao Q;Ding S;Zhang Y;Wei J;Xu G
自噬在宿主对分枝杆菌感染的免疫应答中起着重要作用。结核分枝杆菌(简称结核分枝杆菌)可以通过调节自噬反应来逃避攻击，因此可以生活在巨噬细胞中。MicroRNAs(MiRNAs)是一种非编码的、内源性编码的小RNA，在巨噬细胞功能的精确调控中起着关键作用。在结核分枝杆菌感染过程中，miRNAs是否特异性地影响巨噬细胞自噬的激活在很大程度上尚不清楚。在这项研究中，我们证明了卡介苗感染巨噬细胞后，miRNA-20a的表达增强，通过靶向ATG7和ATG16L1来抑制自噬过程，促进卡介苗在巨噬细胞中的存活。强制过表达miR-20a可降低巨噬细胞中Lc3-II的表达水平和Lc3点数，促进BCG在巨噬细胞中的存活，而miR-20a抑制剂的作用则相反。此外，透射电子显微镜分析进一步证实了miR-20a对自噬的抑制作用。每个细胞截面的自噬小体定量结果显示，miR-20a模拟基因的转染组细胞自噬小体数量显著减少，而miR-20a抑制剂的转染组每细胞截面的自噬小体数量增加。此外，沉默ATG7显著抑制自噬反应，并且ATG7 siRNA和miR-20a模拟基因的联合转染可进一步降低自噬反应。总之，我们的数据显示miR-20a通过靶向ATG7和ATG16L1抑制巨噬细胞的自噬反应并促进卡介苗的存活，这可能对更好地理解结核分枝杆菌感染的发病机制有意义。
Autophagy plays important roles in the host immune response against mycobacterial infection. Mycobacterium tuberculosis (M. tuberculosis) can live in macrophages owing to its ability to evade attacks by regulating autophagic response. MicroRNAs (miRNAs) are small noncoding, endogenously encoded RNA which plays critical roles in precise regulation of macrophage functions. Whether miRNAs specifically influence the activation of macrophage autophagy during M. tuberculosis infection are largely unknown. In this study, we demonstrate that BCG infection of macrophages resulted in enhanced expression of miRNA-20a, which inhibits autophagic process by targeting ATG7 and ATG16L1 and promotes BCG survival in macrophages. Forced overexpression of miR-20a decreased the expression levels of LC3-II and the number of LC3 puncta in macrophages, and promoted BCG survival in macrophages, while transfection with miR-20a inhibitor had the opposite effect. Moreover, the inhibitory effect of miR-20a on autophagy was further confirmed by transmission electron microscopy (TEM) analysis. Quantification of autophagosomes per cellular cross-section revealed a significant reduction upon transfection with miR-20a mimic, but transfection with miR-20a inhibitor increased the number of autophagosomes per cellular cross-section. Moreover, silencing of ATG7 significantly inhibited autophagic response, and transfection with ATG7 siRNA plus miR-20a mimic could further decrease autophagic response. Collectively, our data reveal that miR-20a inhibits autophagic response and promotes BCG survival in macrophages by targeting ATG7 and ATG16L1, which may have implications for a better understanding of pathogenesis of M. tuberculosis infection.
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microRNA-146a 通过抑制一氧化氮的产生来促进巨噬细胞中分枝杆菌的存活。
影响因子：
4.6
作者：
Li M;Wang J;Fang Y;Gong S;Li M;Wu M;Lai X;Zeng G;Wang Y;Yang K;Huang X
通讯作者：
Huang X
影响因子：
30.5
作者：
Ouimet M;Koster S;Sakowski E;Ramkhelawon B;van Solingen C;Oldebeken S;Karunakaran D;Portal-Celhay C;Sheedy FJ;Ray TD;Cecchini K;Zamore PD;Rayner KJ;Marcel YL;Philips JA;Moore KJ
通讯作者：
Moore KJ
影响因子：
11.3
作者：
Gengenbacher M;Kaufmann SH
通讯作者：
Kaufmann SH
DOI：
10.1083/jcb.200412022
发表时间：
2005-05-09
期刊：
The Journal of cell biology
影响因子：
--
作者：
Komatsu M;Waguri S;Ueno T;Iwata J;Murata S;Tanida I;Ezaki J;Mizushima N;Ohsumi Y;Uchiyama Y;Kominami E;Tanaka K;Chiba T
通讯作者：
Chiba T
影响因子：
7.5
作者：
Chekulaeva, Marina;Filipowicz, Witold
通讯作者：
Filipowicz, Witold