MicroRNA-199a Inhibits Cellular Autophagy and Downregulates IFN-β Expression by Targeting TBK1 in Infected Cells.

Front Cell Infect Microbiol

State Key Laboratories for Agrobiotechnology, Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, National Animal Transmissible Spongiform Encephalopathy Laboratory, College of Veterinary Medicine, China Agricultural University, Beijing, China.

Published: August 2019

The mechanism by which microRNAs (miRNAs) modulate innate immunity and autophagy has not been fully elucidated in () infections. In this study, we identified that miR-199a inhibited key innate immune responses and autophagy in murine macrophages infected with . Using and approaches we show that the expression of miR-199a was significantly increased during infection. Furthermore, miR-199a suppressed autophagy and interferon-β (IFN-β) production by directly targeting TANK-binding kinase 1 (TBK1) mRNA in both J774a.1 and BMDM cells. Upregulation of miR-199a or TBK1 silencing (siTBK1) inhibited maturation of autophagosomes and increased survival. Our results demonstrate that, by targeting of TBK1, miR-199a modulates innate immune responses and promote the intracellular survival and growth of .

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6048223PMC
http://dx.doi.org/10.3389/fcimb.2018.00238DOI Listing

Publication Analysis

Top Keywords

targeting tbk1
8
innate immune
8
immune responses
8
mir-199a
5
microrna-199a inhibits
4
inhibits cellular
4
autophagy
4
cellular autophagy
4
autophagy downregulates
4
downregulates ifn-β
4

Similar Publications

TBK1 Targeting Is Identified as a Therapeutic Strategy to Enhance CAR T-Cell Efficacy Using Patient-Derived Organotypic Tumor Spheroids.

Cancer Immunol Res

January 2025

Mass General Cancer Center, Krantz Family Center for Cancer Research, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.

Novel therapeutic strategies are needed to improve the efficacy of chimeric antigen receptor (CAR) T cells as a treatment of solid tumors. Multiple tumor microenvironmental factors are thought to contribute to resistance to CAR T-cell therapy in solid tumors, and appropriate model systems to identify and examine these factors using clinically relevant biospecimens are limited. In this study, we examined the activity of B7-H3-directed CAR T cells (B7-H3.

View Article and Find Full Text PDF

Heme is known to bind to the intrinsically disordered region (IDR) to regulate protein function. The binding of heme to the IDR of transcription factor BACH2 promotes plasma cell differentiation, but the molecular basis is unknown. Heme was found to increase BACH2 IDR interaction with TANK-binding kinase 1 (TBK1).

View Article and Find Full Text PDF

Lysosomes are the major cellular organelles responsible for nutrient recycling and degradation of cellular material. Maintenance of lysosomal integrity is essential for cellular homeostasis and lysosomal membrane permeabilization (LMP) sensitizes toward cell death. Damaged lysosomes are repaired or degraded via lysophagy, during which glycans, exposed on ruptured lysosomal membranes, are recognized by galectins leading to K48- and K63-linked poly-ubiquitination (poly-Ub) of lysosomal proteins followed by recruitment of the macroautophagic/autophagic machinery and degradation.

View Article and Find Full Text PDF
Article Synopsis
  • Endometrial cancer is a serious gynecological issue, and the study focused on the role of TBK1, a kinase involved in inflammation and immunity, in this cancer type.
  • Research found that low TBK1 expression is linked to better patient outcomes, and inhibiting TBK1 with amlexanox reduced cancer cell growth and migration.
  • The effects of amlexanox were shown to work through the AKT/NF-κB signaling pathway, suggesting a new direction for cancer treatments targeting TBK1 in endometrial cancer.
View Article and Find Full Text PDF

DHAV-1 3C protein promotes viral proliferation by antagonizing type I interferon via upregulating the ANXA2 protein.

Int J Biol Macromol

December 2024

Research Center of Avian Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China; International Joint Research Center for Animal Disease Prevention and Control of Sichuan Province, Chengdu 611130, China.; College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China; Key Laboratory of Animal Disease and Human Health of Sichuan Province, Chengdu 611130, China; Engineering Research Center of Southwest Animal Disease Prevention and Control Technology, Ministry of Education of the People's Republic of China, Chengdu 611130, China.

The picornavirus 3C protein plays a crucial role in viral infection. One of its functions is inhibiting the immune response by cleaving or degrading innate immune-related proteins to promote viral infection. Annexin A2 (ANXA2) is a multifunctional host protein that plays a key role in various cellular processes, it also participates in viral infection.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!