School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an, 710000,P.R. China.
Department of Medical Laboratory, School of Clinical Medicine, Ningxia Medical University, Yinchuan, 750004, P.R. China.
J Microbiol Biotechnol. 2019 Jun 28;29(6):989-998. doi: 10.4014/jmb.1811.11062.
Autophagy is crucial for immune defense against (Mtb) infection. Mtb can evade host immune attack and survival within macrophages by manipulating the autophagic process. MicroRNAs (miRNAs) are small, non-coding RNAs that are involved in regulating vital genes during Mtb infection. The precise role of miRNAs in autophagy with the exits of Mtb remains largely unknown. In this study, we found miR-1958, a new miRNA that could regulate autophagy by interacting with 3'UTR of autophagy-related gene 5 (Atg5). In addition, Mtb infection triggered miR-1958 expression in RAW264.7 cells. What's more, miR- 1958 overexpression blocked autophagic flux by impairing the fusion of autophagosomes and lysosomes. Overexpression of miR-1958 reduced Atg5 expression and LC3 puncta while inhibition of miR-1958 brought an increase of Atg5 and LC3 puncta; the opposite results were observed in detection of p62. The survival of Mtb in RAW264.7 cells transfected with mimic of miR-1958 was enhanced. Taken together, our research demonstrated that a novel miR-1958 could inhibit autophagy by interacting with Atg5 and favored intracellular Mtb survival in RAW264.7 cells.
自噬对于（Mtb）感染的免疫防御至关重要。Mtb 可以通过操纵自噬过程来逃避宿主免疫攻击和在巨噬细胞内存活。MicroRNAs（miRNAs）是一种小的非编码 RNA，参与调节 Mtb 感染期间的重要基因。miRNAs 在自噬中的精确作用以及 Mtb 的退出在很大程度上仍然未知。在这项研究中，我们发现了 miR-1958，这是一种新的 miRNA，可以通过与自噬相关基因 5（Atg5）的 3'UTR 相互作用来调节自噬。此外，Mtb 感染在 RAW264.7 细胞中触发了 miR-1958 的表达。更重要的是，miR-1958 的过表达通过破坏自噬体和溶酶体的融合来阻断自噬通量。miR-1958 的过表达降低了 Atg5 表达和 LC3 斑点，而 miR-1958 的抑制则增加了 Atg5 和 LC3 斑点；在检测 p62 时则观察到相反的结果。转染 miR-1958 模拟物的 RAW264.7 细胞中 Mtb 的存活率增加。总之，我们的研究表明，一种新型的 miR-1958 可以通过与 Atg5 相互作用来抑制自噬，并有利于 RAW264.7 细胞内 Mtb 的存活。
