微小RNA-25通过调控NPC1抑制自噬并促进生存。

MiR-25 blunts autophagy and promotes the survival of by regulating NPC1.

作者信息

Dong Wenqi, Wang Gaoyan, Feng Jiajia, Li Pei, Wang Rui, Lu Hao, Lu Wenjia, Wang Chenchen, Wang Xiangru, Chen Huanchun, Xiang Yaozu, Tan Chen

机构信息

State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, China.

Hubei Hongshan Laboratory, Wuhan, Hubei, China.

出版信息

iScience. 2022 Apr 22;25(5):104279. doi: 10.1016/j.isci.2022.104279. eCollection 2022 May 20.

(Mtb) evades host clearance by inhibiting autophagy. MicroRNA-25 (miR-25) expression was significantly up-regulated in the lung tissues of mice infected with Bacillus Calmette-Guerin (BCG) and macrophages infected with Mtb or BCG, especially in the early stages of infection. MiR-25 can significantly increase the survival of Mtb and BCG in macrophages. We validated that miR-25 targets the NPC1 protein located on the lysosomal membrane, resulting in damage to lysosomal function, thereby inhibiting autophagolysosome formation and promoting the survival of Mtb and BCG. Consistently, mice lacking miR-25 exhibited more resistant to BCG infection. In addition, we found that Rv1759c induces the expression of miR-25 through NFKB inhibitor zeta (NFKBIZ). This study demonstrates that the role of miR-25 during Mtb infection contributes to a better understanding of the pathogenesis of tuberculosis (TB).

结核分枝杆菌（Mtb）通过抑制自噬来逃避宿主的清除。在感染卡介苗（BCG）的小鼠肺组织以及感染Mtb或BCG的巨噬细胞中，微小RNA-25（miR-25）的表达显著上调，尤其是在感染的早期阶段。miR-25可显著提高Mtb和BCG在巨噬细胞中的存活率。我们证实miR-25靶向位于溶酶体膜上的NPC1蛋白，导致溶酶体功能受损，从而抑制自噬溶酶体的形成并促进Mtb和BCG的存活。一致的是，缺乏miR-25的小鼠对BCG感染表现出更强的抵抗力。此外，我们发现Rv1759c通过NFKB抑制剂zeta（NFKBIZ）诱导miR-25的表达。这项研究表明miR-25在Mtb感染过程中的作用有助于更好地理解结核病（TB）的发病机制。