MicroRNAs: As Critical Regulators of Tumor- Associated Macrophages
Abstract
:1. Introduction
2. Diverse Strategies Opted by TAMs to Promote Tumor Progression—A Sneak Peek into Molecular Mechanisms
2.1. Proliferation and Growth of Cancer Cells
2.2. Angiogenesis
2.3. Metastasis
2.4. Resistance to Chemotherapy
2.5. Immunosuppression
3. MiRNAs Involved in Regulation of Macrophage Differentiation and Maturation
4. MiRNAs Involved in Macrophage Activation and Polarization
5. MiRNAs Involved in Regulation of Recruitment, Infiltration and Immunosuppressive Function of Macrophages
6. Extracellular MiRNAs Secreted from TAMs
7. Extracellular miRNAs Secreted from Cancer Cells
8. Conclusions and Future Perspective
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
A2AR | Adenosine A2A receptor |
ANG2 | Angiopoietin-2 |
BAK1 | BCL2 antagonist/Killer 1 |
CCL2 | C-C motif chemokine ligand 2 |
CRC | Colorectal cancer |
CSF-1 | Colony-stimulating factor-1 |
EGCG | Epigallocatechin gallate |
EGF | Epidermal growth Factor |
Egr2 | Early growth response protein 2 |
EMT | Epithelial to mesenchymal transition |
EOC | Epithelial ovarian cancer |
EVs | Extracellular vesicles |
GATA-3 | GATA binding protein-3 |
GMP | Granulocyte–monocyte progenitor |
GSK3β | Glycogen synthase kinase 3 beta |
HCC | Hepatocellular carcinoma |
HIF-2α | Hypoxia-inducible factor-2 alpha |
ILs | Interleukins |
MDSCs | Myeloid-derived suppressor cells |
MERTK | MER proto-oncogene, tyrosine kinase |
NF-kB | Nuclear factor kappa-light-chain-enhancer of activated B cells |
NSCLC | Non-small-cell lung carcinoma |
OSCC | Oral squamous cells carcinoma |
PDAC | Pancreatic ductal adenocarcinoma |
PD-L-1 | Programmed death-ligand-1 |
PI3K | Phosphatidylinositol 3-kinase |
PPARδ | Peroxisome proliferator-activated receptor δ |
SOCS3 | Suppressor of cytokine signaling 3 |
STAT-3 | Signal transducer and activator of transcription-3 |
TGCTs | Testicular germ cell tumors |
TGFBR3 | Transforming Growth Factor Beta Receptor 3 |
TLR | Toll like receptor |
TNF-α | Tumor-necrosis factor-α |
TWIST1 | Twist-related protein 1 |
uPA | Urokinase-type plasminogen activator |
VEGF | Vascular endothelial growth factor |
WNT5B | Wnt family member 5B |
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miRNAs Involved in Macrophage Polarization | Function | Reference |
---|---|---|
miR-375 | Facilitates macrophage recruitment, M2-like phenotype and tumor progression | [71] |
miR-23a/miR-27a/miR24-2 cluster | Promote M1-like phenotype, inhibit M2-like phenotype in breast cancer | [72] |
miR-340-5p | Promotes M2 polarization in glioblastoma | [73] |
miR-155, miR-125b-2 | Macrophage re-programming to M1-like phenotype in pancreatic cancer | [74] |
miR-29a-3p | Promotes M2 polarization in OSCC | [75] |
miR-222-3p | Promotes M2-like phenotype in ovarian cancer | [76] |
miR-940 | Promotes M2 polarization in epithelial ovarian cell carcinoma | [77] |
miR-203 | Promotes M2 polarization and metastasis in CRC | [78] |
miR-145 | Promotes M2-like phenotype in CRC | [79] |
miR-16 | Promotes M1-like phenotype in breast cancer | [80] |
miR-103a | Increases M2 polarization in lung cancer | [81] |
miR-21-3p, miR-181d-5p, miR-125b -5p | Promote M2 polarization, cancer cell migration, proliferation in EOC | [82] |
miR-301a-3p | Enriches M2-like macrophages via modulating PTEN/PI3Kγ axis in pancreatic cancer | [83] |
miR-132, miR-29b-1, miR-27a, miR-146a, miR-222 | Higher expression of these miRNAs promote M2b-like phenotype | [59,84] |
miR-let7a, miR-320a, miR-146a | Promote M2-like phenotype | [85,86,87] |
miR-142-3p | Inhibit M2 polarization, reduces tumor growth in HCC | [88,89] |
let-7c | Inhibits M1 polarization and promote M2-like phenotype | [90] |
miR-1246 | Promote M2 polarization via modulating STAT3 and NF-κB axis. | [88,91] |
let-7d-5p | Promote M2-like phenotype | [16] |
miR-451, miR-21 | Influence macrophage polarization in glioblastoma | [92] |
Extracellular miRNAs Secreted from Cancer Cells Regulating Cancer Progression or Chemoresistance | Function | Reference |
miR-221, miR-222 | Promote tamoxifen resistance in breast tumor cells | [93] |
miR-1246 | Imparts chemoresistance in ovarian cancer cells | [94] |
miR-21 | Induces chemoresistance in neuroblastoma, enhances miR-155 expression | [95] |
miR-23a-3p | Promotes tumor cell escape via impairing T-cell function | [96] |
miR-204-5p | Regulates cisplatin resistance in EOC | [97] |
miR-let7a | Creates an immunosuppressive environment by enhancing the expression of M2-like phenotype associated genes | [85] |
miR-142-3p | Induces malignant phenotype in oral carcinoma | [98] |
miR-105 | Promotes tumor progression and metastasis via degrading vascular endothelial barriers | [99] |
miR-214 | Promotes tumor growth via deregulating PTEN and impairing T-cell function in mouse model | [100] |
miR-21, miR-29a | Induces inflammatory response in NSCLC cells via activating NF-kB pathway | [101] |
Extracellular miRNAs Derived from TAMs Regulating Cancer Progression or Chemoresistance | Function | Reference |
miR-7 | Inhibits metastasis in EOC via modulating EGFR/AKT/ERK1/2 axis | [102] |
miR-365 | Promotes gemcitabine chemoresistance in PDAC | [103] |
miR-29a-3p, miR-21-5p | Establish an immunosuppressive environment in EOC | [104] |
miR-155-5p, miR-21-5p | Increase migration and invasion of colon cancer cells via downregulating BRG 1 | [105] |
miR-125a/b | Negatively influence tumor cell division and stemness properties of HCC via targeting CD90 | [106] |
miR-21 | Induces chemoresistance in gastric cancer | [107] |
miR-501-3p | Progression of PDAC via modulating TGF-β | [108] |
miR-223 | Imparts cisplatin resistance in EOC | [109] |
miRNAs Involved in Macrophage Differentiation and Maturation | Function | Reference |
miR-155, miR-146a, miR-338, and miR-342 | Facilitate the progression of HSCs differentiation process | [66] |
miR-17-92 cluster: miR-18a, miR-17, miR-92a, miR-19a, miR-19b-1, miR-20a | Inhibition of their expression by PU.1 promote HSCs differentiation | [67] |
miR-146a, miR-126, miR-29a, miR-155, miR-130a, miR-125a/b, miR-338, miR-342, miR-21, miR-196b | Mediate differentiation and maturation of HSCs by regulating expression of various target genes | [61,63,64,66,69,110] |
miRNAs Regulating Recruitment of Macrophages at Tumor Site | Function | Reference |
miR148b | Inhibits TAM infiltration in tumor | [111] |
miR-375 | Induces TAM infiltration in breast cancer | [71] |
miR-125b | Reduces recruitment of macrophages at tumor site | [112] |
Subtype | Functions | Key Activating Stimuli | Markers | References |
---|---|---|---|---|
M2a | Anti-inflammatory and tissue repair, killing of the infectious parasites | M-CSF, IL-13, IL-14 | CD206, MHC-II, FZZI, CD163, Arg-1, IL-10, TGF-β, WNT5b | [117,118,119,120,121,122,123,124] |
M2b | Increases infection, immunoregulation, tumor growth and progression | TLR, IL-1R antagonist, immunocomplexes | CD206, CD86, IL-6, IL-1, IL-10 TNF-α | |
M2c | Immunosuppression, phagocytosis, tissue remodeling, matrix deposition, and efferocytosis | IL-10, glucocorticoids | CD206, CD163, IL-10, MERTK, ECM, TGF-β | |
M2d | Angiogenesis, anti and pro-tumoral properties | A2AR ligands, TLR, IL-6 | IL-10, IL-12, VEGF, TGF-β |
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Chatterjee, B.; Saha, P.; Bose, S.; Shukla, D.; Chatterjee, N.; Kumar, S.; Tripathi, P.P.; Srivastava, A.K. MicroRNAs: As Critical Regulators of Tumor- Associated Macrophages. Int. J. Mol. Sci. 2020, 21, 7117. https://doi.org/10.3390/ijms21197117
Chatterjee B, Saha P, Bose S, Shukla D, Chatterjee N, Kumar S, Tripathi PP, Srivastava AK. MicroRNAs: As Critical Regulators of Tumor- Associated Macrophages. International Journal of Molecular Sciences. 2020; 21(19):7117. https://doi.org/10.3390/ijms21197117
Chicago/Turabian StyleChatterjee, Bilash, Priyanka Saha, Subhankar Bose, Devendra Shukla, Nabanita Chatterjee, Sanjay Kumar, Prem Prakash Tripathi, and Amit Kumar Srivastava. 2020. "MicroRNAs: As Critical Regulators of Tumor- Associated Macrophages" International Journal of Molecular Sciences 21, no. 19: 7117. https://doi.org/10.3390/ijms21197117