Table 3.
miRNAs influencing multiple host cell death pathways in M. tuberculosis infection
| miRNA | Remarks | Cell Death Pathway | Reference |
|---|---|---|---|
| miR-155 | Highly overexpressed in Mtb infected mice 30-day postinfection | Apoptosis | (350) |
| ESAT-6 promotes apoptosis of macrophages through miR-155-SOCS1 interaction | (351) | ||
| Inhibits apoptosis of infected cells by targeting FOXO3 | (352) | ||
| Induces apoptosis following BCG infection | (353) | ||
| miR-155-5p | Promotes the intracellular Mtb replication during early innate immune responses and helps the survival of infected macrophages | Apoptosis | (354, 355) |
| miR-196b | Increased expression in patients with active TB and functions as a marker for active TB | Apoptosis | (356) |
| Induces apoptosis by targeting c-Myc and Bcl2 | (357) | ||
| miR-325-3p | Promotes Mtb persistence and latency in the host cell | Apoptosis | (358) |
| Inhibits apoptosis through activation of STAT3 signaling | (359) | ||
| miR-20a-5p | Downregulated by Mtb infection, triggers cell apoptosis to facilitate mycobacterial clearance through targeting JNK2 in human macrophages | Apoptosis | (360) |
| miR-708 | Upregulated in sera of patients with TB | Apoptosis | (361) |
| Induces apoptosis by targeting E-cadherin regulators | (362) | ||
| miR-let-7e | Inhibits apoptosis by targeting the executioner of programmed cell death Caspase-3 | Apoptosis | (363) |
| miR-29a | Inhibits apoptosis upon mycobacterial infection via Caspase-3 and -7 | Apoptosis | (363) |
| miR-582-5p | Upregulated in patients with active TB, inhibits apoptosis of monocytes by targeting FOXO1 | Apoptosis | (364) |
| miR-21 | Inhibits apoptosis, targets several genes of both intrinsic and extrinsic apoptosis pathways | Apoptosis | (365) |
| Decreased expression in CD4 T cells and peripheral blood of patients with TB | (366) | ||
| Functions as a key switch in the inflammatory response | (367) | ||
| Inhibits apoptosome formation by targeting Bcl-2 pathway | (64) | ||
| miR-145 | Downregulation of miR-145 leads to overexpression of its targets and inhibition of apoptosis | Apoptosis | (368) |
| miR-125b | Mtb lipomannan destabilizes TNF biosynthesis by miR-125b regulation | Apoptosis | (369) |
| miR-223 | Upregulated in patients with active TB and inhibits apoptosis of macrophages by targeting FOXO3 | Apoptosis | (370) |
| miR-27b | Modulates inflammatory response and apoptosis upon Mtb infection | Apoptosis | (371) |
| miR-155 | Promotes autophagy to eliminate intracellular Mtb by targeting Rheb | Autophagy | (261) |
| miR-99b | Downregulates the production of TNF-α and TNF-α receptor | Autophagy | (372) |
| miR-26a | Impairs Mtb survival in macrophages by targeting the transcription factor Klotho-like factor-4 (KLF4) | Autophagy | (373) |
| miR-23a-5p | Overexpression of miR-23a-5p prevented Mtb-induced autophagy in macrophages by modulating TLR2/MyD88/NF-κB signaling | Autophagy | (374) |
| miR-33 | Enables Mtb intracellular survival and persistence inside the host | Autophagy | (375) |
| Targets autophagy effectors (ATG5, ATG12, LC3B and LAMP1), inhibits autophagy, and reprogram host lipid metabolism | (375) | ||
| miR-27a-5p | Downregulates Ca2+ signaling leading to inhibition of autophagosome formation and xenophagy; promotes intracellular survival of Mtb | Autophagy | (376) |
| miR-144-3p | Inhibits autophagy activation by targeting ATG4 in RAW264.7 macrophages | Autophagy | (377) |
| miR-144-5p | Inhibits phagosome maturation and T cell function | Autophagy | (378) |
| Upregulated in human MDMs upon Mtb infection | (379) | ||
| Targets the 3′-UTR of DNA damage-regulated autophagy modulator 2 (DRAM2) in PBMC-derived macrophages and THP-1 cells | (379) | ||
| miR-889-5p | Overexpression inhibits autophagy and maintains bacterial survival in granulomas | Autophagy | (380) |
| miR-125a | Increases robustly in TB and inhibits autophagy by targeting UVRAG and anti-microbial responses | Autophagy | (381) |
| miR-30a | Inhibits autophagy and promotes Mtb survival mechanism in human macrophages by targeting Beclin-1 | Autophagy | (382) |
| miR-3619-5p | Targets cathepsin S and affects autophagy in THP-1 macrophages | Autophagy | (383) |
| miR-17-5p | Involved in autophagy by targeting ULK-1, controls the survival of mycobacteria in macrophages | Autophagy | (384) |
| Regulates autophagy in Mtb-infected macrophages by targeting Mcl-1 and STAT3 | (385) | ||
| miR-20a | Inhibits autophagy by targeting ATG7 and ATG16L1 and promotes mycobacterial survival in macrophages | Autophagy | (386) |
| miR-142-3p | Inhibits autophagy upon Mtb infection, targets N-Wasp leading to reduced phagocytosis | Autophagy | (387) |
| miR-20b | Inhibits Mtb-induced inflammation in mouse lung by targeting NLRP3 | Pyroptosis | (388) |
Several miRNAs are regulated following mycobacterial infection from several in vitro and in vivo studies. ATG, autophagy related; Bcl2, B-cell leukemia/lymphoma-2; ESAT-6, early secreted antigenic target of 6 kDa; LC3, light chain 3; MDM, monocyte-derived macrophages; Mtb, Mycobacterium tuberculosis; NLRP3, NOD-, LRR- and pyrin domain-containing protein 3; PBMC, peripheral blood mononuclear cell; TB, tuberculosis.