Induction and regulatory function of miR-9 in human monocytes and neutrophils exposed to proinflammatory signals
Open accessAbstract
Inflammation involves a coordinated, sequential, and self limiting sequence of events controlled by positive and negative regulatory mechanisms. Recent studies have shown that microRNAs (miRNAs), an evolutionarily conserved class of endogenous 22-nucleotide noncoding RNAs, contribute to the regulation of inflammation by repressing gene expression at the posttranscriptional level. In this study, we characterize the profile of miRNAs induced by LPS in human polymorphonuclear neutrophils (PMN) and monocytes. In particular, we identify miR-9 as the only miRNA (among 365 analyzed) up-regulated in both cell types after TLR4 activation. miR-9 is also induced by TLR2 and TLR7/8 agonists and by the proinflammatory cytokines TNF-alpha and IL-1beta, but not by IFNgamma. Among the 3 different genes encoding miR-9 precursors in humans, we show that LPS selectively induces the transcription of miR-9-1 located in the CROC4 locus, in a MyD88- and NF-kappaB-dependent manner. In PMN and monocytes, LPS regulates NFKB1 at both the transcriptional and posttranscriptional levels, and a conserved miR-9 seed sustained a miR-9-dependent inhibition of the NFKB1 transcript. Overall, these data suggest that TLR4-activated NF-kappaB rapidly increases the expression of miR-9 that operates a feedback control of the NF-kappaB-dependent responses by fine tuning the expression of a key member of the NF-kappaB family.
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NF-κB activation by LPS initiates transcription of miR-9-1, which subsequently downregulates NF-κB.
“It was shown that NF-κB, upon its activation in response to LPS, initiates transcription of miR-9-1, which subsequently downregulates NF-κB [112].”
From MicroRNAs as Regulators of Phagocytosis (2022) · cites this paper as [112]
The Results show that LPS-induced miR-9-1 transcription depends on NF-κB and that miR-9 reduces NFKB1/p105 expression in human monocytes. The paper proposes feedback control of NF-κB-dependent responses, but it does not show that miR-9 downregulates NF-κB as a whole. The supplied passages have section labels but no page numbers. (LLM, conf=0.85)
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BackgroundInfluentialTLR2 Expression Is Regulated by MicroRNA miR-19 in Rheumatoid Fibroblast-like Synoviocytes
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MicroRNAs: Master Regulators of Ethanol Abuse and Toxicity?
Miranda, R. C., Pietrzykowski, A. Z., Tang, Y., Sathyan, P., Mayfield, D., Keshavarzian, A., Sampson, W., & Hereld, D. (2010) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.2009.01126.x · Cited by 178 · see citing works
“For example, a recent report (Bazzoni et al., 2009) showed that miR9 was up-regulated in human neutrophils and monocytes, when stimulated by TLR4 or the proinflammatory cytokines, TNF-a and interleukin-1b.”
BackgroundInhibitory feedback control of NF-κB signalling in health and disease
Prescott, J. A., Mitchell, J. P., & Cook, S. J. (2021) · Biochemical Journal · doi:10.1042/bcj20210139 · Cited by 193 · see citing works
OmicsNet: a web-based tool for creation and visual analysis of biological networks in 3D space
Zhou, G., & Xia, J. (2018) · Nucleic Acids Research · doi:10.1093/nar/gky510 · Cited by 175 · see citing works
“Sp1 is a transcription factor involved in the regulation of Il-10 (44), a key effector in regulatory T cell response that mediates helminth-mediated immunoregulation (45), while the miRNA-9 family is involved in the regulation of the immune response (46,47).”
BackgroundEmerging Roles of microRNAs in Ischemic Stroke: As Possible Therapeutic Agents
Khoshnam, S. E., Winlow, W., Farbood, Y., Moghaddam, H. F., & Farzaneh, M. (2017) · Journal of Stroke · doi:10.5853/jos.2016.01368 · Cited by 156 · see citing works
The Clinical Application of MicroRNAs in Infectious Disease
Drury, R. E., O’Connor, D., & Pollard, A. J. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.01182 · Cited by 169 · see citing works
MicroRNAs in inflammatory lung disease - master regulators or target practice?
Oglesby, I. K., McElvaney, N. G., & Greene, C. M. (2010) · Respiratory Research · doi:10.1186/1465-9921-11-148 · Cited by 145 · see citing works
“miR-155, -146, -9 and -21 to name a few, which were shown to target SHIP1, IRAK1/TRAF6, NF- B1, and tumor suppressor PDCD4 respectively [54-57].”
Transcriptional firing helps to drive NETosis
Khan, M. A., & Palaniyar, N. (2017) · Scientific Reports · doi:10.1038/srep41749 · Cited by 172 · see citing works
MiR-9 promotes microglial activation by targeting MCPIP1
Yao, H., Ma, R., Yang, L., Hu, G., Chen, X., Duan, M., Kook, Y., Niu, F., Liao, K., Fu, M., et al. (2014) · Nature Communications · doi:10.1038/ncomms5386 · Cited by 156 · see citing works
Microbiotadown regulates dendritic cell expression of miR-10a which targets IL-12/IL-23p40
Xue, X., Feng, T., Yao, S.-X., Wolf, K. J., Liu, C.-G., Liu, X.-P., Elson, C., & Cong, Y. (2011) · Journal of Immunology · doi:10.4049/jimmunol.1100535 · Cited by 155 · see citing works
MicroRNA Dysregulation in the Spinal Cord following Traumatic Injury
Yunta, M., Nieto‐Díaz, M., Esteban, F. J., Caballero-López, M. J., Navarro-Ruíz, R., Reigada, D., Pita-Thomas, D. W., del Águila, Á., Muñoz‐Galdeano, T., & Maza, R. M. (2012) · PLoS ONE · doi:10.1371/journal.pone.0034534 · Cited by 147 · see citing works
MicroRNAs in the immune response
Pedersen, I. M., & David, M. (2008) · Cytokine · doi:10.1016/j.cyto.2008.07.016 · Cited by 139 · see citing works
miRNAs reshape immunity and inflammatory responses in bacterial infection
Zhou, X., Li, X., & Wu, M. (2018) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-018-0006-9 · Cited by 183 · see citing works
Zeng, Z., Gong, H., Li, Y., Jie, K., Ding, C., Shao, Q., Liu, F., Zhan, Y., Nie, C. X., Zhu, W., et al. (2013) · Experimental Lung Research · doi:10.3109/01902148.2013.808285 · Cited by 150 · see citing works
microRNAs in Inflammatory Bowel Disease
Pekow, J., & Kwon, J. (2011) · Inflammatory Bowel Diseases · doi:10.1002/ibd.21691 · Cited by 141 · see citing works
“Similarly, miR-9 is induced by TLR4 activated nuclear factor kappa B (NF-jB) in polymorphonuclear cells and monocytes, and miR-9 is involved in inhibitory feedback at the level of NFKB1, a gene that contributes to NF-jB protein expression.(30) In addition to miR-146a and miR-9, miR-155 plays in integral role in the im…”
BackgroundInterplay Between Reactive Oxygen Species and MicroRNAs in Cancer
He, J., & Jiang, B. (2016) · Current Pharmacology Reports · doi:10.1007/s40495-016-0051-4 · Cited by 141 · see citing works
Perry, M. M., Williams, A. E., Tsitsiou, E., Larner-Svensson, H., & Lindsay, M. A. (2009) · FEBS Letters · doi:10.1016/j.febslet.2009.09.038 · Cited by 116 · see citing works
Moffatt, C. E., & Lamont, R. J. (2011) · Infection and Immunity · doi:10.1128/iai.00082-11 · Cited by 135 · see citing works
“Human monocytes exposed to lipopolysaccharide (LPS) upregulate miRNA-146a (miR-146a) and miR-9, resulting in the downregulation of cytokines involved in the innate immune response (5, 54).”
BackgroundMicroRNA dysregulation in spinal cord injury: causes, consequences and therapeutics
Nieto‐Díaz, M., Esteban, F. J., Reigada, D., Muñoz‐Galdeano, T., Yunta, M., Caballero-López, M. J., Navarro-Ruíz, R., del Águila, Á., & Maza, R. M. (2014) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2014.00053 · Cited by 135 · see citing works
“In particular, downregulation of miR-9 and miR-199 (Yunta et al., 2012) may induce the overexpression of the NF-κB pathway genes p50NFkB and ikkb (Chen et al., 2008; Bazzoni et al., 2009; Wang et al., 2011).”
BackgroundGao, F., Zhao, Z.-L., Zhao, W.-T., Fan, Q., Wang, S.-C., Li, J., Zhang, Y.-Q., Shi, J.-W., Lin, X.-L., Yang, S., et al. (2013) · Biochemical and Biophysical Research Communications - BBRC · doi:10.1016/j.bbrc.2012.12.097 · Cited by 133 · see citing works
Cerella, C., Sobolewski, C., Dicato, M., & Diederich, M. (2010) · Biochemical Pharmacology · doi:10.1016/j.bcp.2010.06.050 · Cited by 129 · see citing works
MicroRNAs in the regulation of TLR and RIG-I pathways
Li, Y., & Shi, X. (2012) · Cellular and Molecular Immunology · doi:10.1038/cmi.2012.55 · Cited by 125 · see citing works
MicroRNA regulation of innate immune responses in epithelial cells
Zhou, R., O’Hara, S. P., & Chen, X. (2011) · Cellular and Molecular Immunology · doi:10.1038/cmi.2011.19 · Cited by 111 · see citing works
“26 Additionally, LPS directly induces miR-9 expression via the myeloid differentiation primary response gene 88 (MyD88)/NF-kB-dependent pathway in human neutrophils, monocytes and macrophages”
BackgroundMicroRNAs as regulators of death receptors signaling
Garofalo, M., Condorelli, G. L., Croce, C. M., & Condorelli, G. (2009) · Cell Death and Differentiation · doi:10.1038/cdd.2009.105 · Cited by 120 · see citing works
Teruel, R., Pérez-Sánchez, C., Corral, J., Herranz, M. T., Pérez-Andreu, V., Saiz, E., García-Barberá, N., Martínez-Martínez, I., Roldán, V., Vicente, V., et al. (2011) · Journal of Thrombosis and Haemostasis · doi:10.1111/j.1538-7836.2011.04451.x · Cited by 120 · see citing works
Wu, X.-Q., Dai, Y., Yang, Y., Huang, C., Meng, X.-M., Wu, B.-M., & Li, J. (2016) · Immunology · doi:10.1111/imm.12608 · Cited by 117 · see citing works
The emerging role of micro RNA s in regulating immune and inflammatory responses in the lung
Foster, P. S., Plank, M. W., Collison, A., Tay, H. L., Kaiko, G. E., Li, J., Johnston, S. L., Hansbro, P. M., Kumar, R. K., Yang, M., et al. (2013) · Immunological Reviews · doi:10.1111/imr.12058 · Cited by 109 · see citing works
“Let-7a 4 Up KBRAS2 Positive regulator of NF-jB signaling (25) Let-7e 4 Up TLR4 Negative regulator of TLR4 signaling (26) Mir-9 2, 4, 7, 8 Up NFKB1 Negative regulator of NF-jB signaling (14) Mir-21 4 Up PDCD4 Negative regulator of TLR4 signaling (6) Mir-125b 4 Down IRF4, KBRAS2 and TNF Positive regulation of TNF-a resp…”
Background
- Authors
- Bazzoni, F., Rossato, M., Fabbri, M., Gaudiosi, D., Mirolo, M., Mori, L., Tamassia, N., Mantovani, A., Cassatella, M. A., & Locati, M.
- Affiliations
- University of Verona (IT)
- Humanitas University (IT)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2009-03-31
- Volume
- 106
- Issue
- 13
- Pages
- 5282-5287
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2664036
- OpenAlex
- W2020932061
- Cited by
- 548
- References
- 40
- Citations by year
- 2026: 7 · 2025: 6 · 2024: 17 · 2023: 14 · 2022: 18 · 2021: 25 · 2020: 33 · 2019: 33 · 2018: 38 · 2017: 38 · 2016: 35 · 2015: 36 · 2014: 46 · 2013: 65 · 2012: 50
- FWCI
- 19.41
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Fondazione Cariplo
- Associazione Italiana per la Ricerca sul Cancro
- Fondazione Cassa di Risparmio di Verona Vicenza Belluno e Ancona
- Università degli Studi di Verona
- Alleanza Contro il Cancro
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Keywords
- miR-9, microRNA, monocytes, neutrophils, lipopolysaccharide, TLR4, TLR2, TLR7/8, NF-κB, NFKB1, MyD88, post-transcriptional regulation, inflammation, TNF-α, IL-1β, feedback regulation
- MeSH terms
- Humans, Inflammation, Lipopolysaccharides, Monocytes, Neutrophils, Transcriptional Activation, Cytokines, NF-kappa B, Inflammation Mediators, Gene Expression Profiling, MicroRNAs, Toll-Like Receptors, Toll-Like Receptor 4
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