The miR-100-5p Targets SMARCA5 to Regulate the Apoptosis and Intracellular Survival of BCG in Infected THP-1 Cells

Li Su; Tingting Zhu; Han Liu; Yifan Zhu; Yongchong Peng; Tian Tang; Shiying Zhou; Changmin Hu; Huanchun Chen; Aizhen Guo; Yingyu Chen

doi:10.3390/cells12030476

The miR-100-5p Targets SMARCA5 to Regulate the Apoptosis and Intracellular Survival of BCG in Infected THP-1 Cells

Cells. 2023 Feb 1;12(3):476. doi: 10.3390/cells12030476.

Authors

Li Su^{1

2}, Tingting Zhu^{1

2}, Han Liu^{1

2}, Yifan Zhu^{1

2}, Yongchong Peng^{1

2}, Tian Tang^{1

2}, Shiying Zhou^{1

2}, Changmin Hu^{1

2}, Huanchun Chen^{1

2}, Aizhen Guo^{1

2

3

4}, Yingyu Chen^{1

2

3

4}

Affiliations

¹ The State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China.
² Key Laboratory of Development of Veterinary Diagnostic Products, Ministry of Agriculture and Rural Affairs, Huazhong Agriculture University, Wuhan 430070, China.
³ National Professional Laboratory for Animal Tuberculosis (Wuhan), Ministry of Agriculture and Rural Affairs, Huazhong Agriculture University, Wuhan 430070, China.
⁴ Hubei International Scientific and Technological Cooperation Base of Veterinary Epidemiology, Hubei Hongshan Laboratory, Huazhong Agricultural University, Wuhan 430070, China.

Abstract

Mycobacterium tuberculosis (M. tb) is the causative agent of tuberculosis (TB) that leads to millions of deaths each year. Extensive evidence has explored the involvement of microRNAs (miRNAs) in M. tb infection. Limitedly, the concrete function of microRNA-100-5p (miR-100-5p) in M. tb remains unexplored and largely elusive. In this study, using Bacillus Calmette-Guérin (BCG) as the model strain, we validated that miR-100-5p was significantly decreased in BCG-infected THP-1 cells. miR-100-5p inhibition effectively facilitated the apoptosis of infected THP-1 cells and reduced BCG survival by regulating the phosphatidylinositol 3-kinase/AKT pathway. Further, SMARCA5 was the target of miR-100-5p and reduced after miR-100-5p overexpression. Since BCG infection down-regulated miR-100-5p in THP-1 cells, the SMARCA5 expression was up-regulated, which in turn increased apoptosis through caspase-3 and Bcl-2 and, thereby, reducing BCG intracellular survival. Collectively, the study uncovered a new molecular mechanism of macrophage to suppress mycobacterial infection through miR-100-5p and SMARCA5 pathway.

Keywords: BCG; SMARCA5; THP-1; apoptosis; miR-100-5p; survival.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adenosine Triphosphatases
Apoptosis
BCG Vaccine
Chromosomal Proteins, Non-Histone
Humans
MicroRNAs* / metabolism
Mycobacterium bovis* / metabolism
THP-1 Cells
Tuberculosis* / microbiology

Substances

BCG Vaccine
MicroRNAs
SMARCA5 protein, human
Adenosine Triphosphatases
Chromosomal Proteins, Non-Histone
MIRN100 microRNA, human

Grants and funding

The work was funded by the National Key Research and Development Programme of China (grant no. 2021YFD1800403), the National Natural Science Foundation of China (grant no. U21A20259), the Natural Science Foundation of Hubei Province (grant no. 2021CFA016) and the China Agricultural Research System (grant no. CARS-37).