The circ_0074371/miR-4738-3p/AMPK Signaling Axis Induces M1 Macrophage Polarization and Restricts Intracellular Survival of Mycobacterium tuberculosis
- 1The First Dongguan Affiliated Hospital of Guangdong Medical University
Abstract
Tuberculosis, an infectious disease caused by Mycobacterium tuberculosis, remains endemic in regions where it is prevalent. Mycobacterium tuberculosis is an intracellular pathogen that can survive within host macrophages; however, the mechanisms governing its long-term persistence and the progression to active pulmonary tuberculosis remain poorly understood. Circular RNAs (circRNAs) have been implicated in the initiation and progression of numerous diseases. In our previous study, circRNA sequencing identified several circRNAs associated with tuberculosis progression. In the present study, sequencing and reverse transcription-polymerase chain reaction (RT-PCR) analyses revealed that Circ_0074371 was significantly downregulated in monocytes from patients with active pulmonary tuberculosis (ATB) and was closely associated with disease onset and progression, exhibiting considerable diagnostic value for ATB. Functional experiments further showed that Circ_0074371 significantly impaired the intracellular survival of Mtb and promoted M1 macrophage polarization. Mechanistically, Circ_0074371 acted as a competing endogenous RNA by sequestering miR-4738-3p, a potent negative regulator of AMP-activated protein kinase (AMPK) activation. Collectively, these findings identify Circ_0074371 as a tuberculosis-associated circRNA that regulates AMPK activity and reveal a novel mechanism through which Circ_0074371 influences macrophage polarization via the AMPK pathway, providing new insights into potential therapeutic targets for ATB.
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BibTeX
@misc{zhang2026circ0074371mir47383pampk,
title = {{The circ_0074371/miR-4738-3p/AMPK Signaling Axis Induces M1 Macrophage Polarization and Restricts Intracellular Survival of Mycobacterium tuberculosis}},
author = {J.-a. Zhang and C.-Y. Lian and Y.-B. Lu and S.-Y. Yao and H. Xu and Y. Xu and G.-B. Liu and G.-S. Chen and Y.-F. Cen and Y.-T. Li and Z.-L. Xu and Y.-D. Huang and G.-Y. Chen and J.-J. Wang and J.-H. Shi and Y.-C. Gao and X.-Z. Cai and J. Liang and W.-C. Huang and Z.-P. Zhang and J. Pi and J.-F. Xu},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.20.760595},
url = {https://www.biorxiv.org/content/10.64898/2026.10.20.760595v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - The circ_0074371/miR-4738-3p/AMPK Signaling Axis Induces M1 Macrophage Polarization and Restricts Intracellular Survival of Mycobacterium tuberculosis
AU - J.-a. Zhang
AU - C.-Y. Lian
AU - Y.-B. Lu
AU - S.-Y. Yao
AU - H. Xu
AU - Y. Xu
AU - G.-B. Liu
AU - G.-S. Chen
AU - Y.-F. Cen
AU - Y.-T. Li
AU - Z.-L. Xu
AU - Y.-D. Huang
AU - G.-Y. Chen
AU - J.-J. Wang
AU - J.-H. Shi
AU - Y.-C. Gao
AU - X.-Z. Cai
AU - J. Liang
AU - W.-C. Huang
AU - Z.-P. Zhang
AU - J. Pi
AU - J.-F. Xu
PY - 2026
DA - 2026/10/20
PB - bioRxiv
DO - 10.64898/2026.10.20.760595
UR - https://www.biorxiv.org/content/10.64898/2026.10.20.760595v1
AB - Tuberculosis, an infectious disease caused by Mycobacterium tuberculosis, remains endemic in regions where it is prevalent. Mycobacterium tuberculosis is an intracellular pathogen that can survive within host macrophages; however, the mechanisms governing its long-term persistence and the progression to active pulmonary tuberculosis remain poorly understood. Circular RNAs (circRNAs) have been implicated in the initiation and progression of numerous diseases. In our previous study, circRNA sequencing identified several circRNAs associated with tuberculosis progression. In the present study, sequencing and reverse transcription-polymerase chain reaction (RT-PCR) analyses revealed that Circ_0074371 was significantly downregulated in monocytes from patients with active pulmonary tuberculosis (ATB) and was closely associated with disease onset and progression, exhibiting considerable diagnostic value for ATB. Functional experiments further showed that Circ_0074371 significantly impaired the intracellular survival of Mtb and promoted M1 macrophage polarization. Mechanistically, Circ_0074371 acted as a competing endogenous RNA by sequestering miR-4738-3p, a potent negative regulator of AMP-activated protein kinase (AMPK) activation. Collectively, these findings identify Circ_0074371 as a tuberculosis-associated circRNA that regulates AMPK activity and reveal a novel mechanism through which Circ_0074371 influences macrophage polarization via the AMPK pathway, providing new insights into potential therapeutic targets for ATB.
ER -