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Cited by 496MicroRNA in disease regulationImmune Response and InflammationMacrophage Migration Inhibitory Factor

Turning 21: Induction of miR-21 as a Key Switch in the Inflammatory Response

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Sheedy, Frederick J.·2015·Frontiers in Immunology
DOI 10.3389/fimmu.2015.00019PMC PMC4310327
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Abstract

miR-21 is one of the most highly expressed members of the small non-coding microRNA family in many mammalian cell types. Its expression is further enhanced in many diseased states including solid tumors, cardiac injury, and inflamed tissue. While the induction of miR-21 by inflammatory stimuli cells has been well documented in both hematopoietic cells of the immune system (particularly monocytes/macrophages but also dendritic and T-cells) and non-hematopoietic tumorigenic cells, the exact functional outcome of this elevated miR-21 is less obvious. Recent studies have confirmed a key role for miR-21 in the resolution of inflammation and in negatively regulating the pro-inflammatory response induced by many of the same stimuli that trigger miR-21 induction itself. In particular, miR-21 has emerged as a key mediator of the anti-inflammatory response in macrophages. This suggests that miR-21 inhibition in leukocytes will promote inflammation and may enhance current therapies for defective immune responses such as cancer, mycobacterial vaccines, or Th2-associated allergic inflammation. At the same time, miR-21 has been shown to promote inflammatory mediators in non-hematopoietic cells resulting in neoplastic transformation. This review will focus on functional studies of miR-21 during inflammation, which is complicated by the numerous molecular targets and processes that have emerged as miR-21 sensitive. It may be that the exact functional outcome of miR-21 is determined by multiple features including the cell type affected, the inducing signal, the transcriptomic profile of the cell, which ultimately affect the availability and ability to engage different target mRNAs and bring about its unique responses. Reviewing this data may illustrate that RNA-based oligonucleotide therapies for different diseases based upon miR-21 may have to target the unique and operative miRNA:mRNA interactions' functionally active in disease.

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Authors
Sheedy, F. J.
Affiliations
Trinity College Dublin (IE)
Corresponding author
Sheedy, Frederick J.
ORCID
Sheedy, Frederick J.
Venue
Frontiers in Immunology
Publisher
Frontiers Media SA
Published
2015-01-29
Volume
6
Pages
19-19
ISSN
1664-3224 (ISSN-L)
DOI
10.3389/fimmu.2015.00019
PMC
PMC4310327
OpenAlex
W2076862753
Cited by
496
References
7
Citations by year
2026: 25 · 2025: 42 · 2024: 39 · 2023: 36 · 2022: 53 · 2021: 88 · 2020: 57 · 2019: 43 · 2018: 38 · 2017: 34 · 2016: 28 · 2015: 12
FWCI
3.64
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Frontiers in Immunology (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Arrow@dit (Dublin Institute of Technology) (acceptedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Trinity's Access to Research Output (TARA) (Trinity College Dublin) (submittedVersion, cc-by-nc-sa)
Funders
Science Foundation Ireland (13/SIRG/2136)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
  • Life Sciences › Immunology and Microbiology › Immunology › Macrophage Migration Inhibitory Factor
Keywords
miR-21, microRNA, inflammation, anti-inflammatory response, macrophages, inflammation resolution, pro-inflammatory signaling, miRNA target mRNAs, oncogenic transformation, cancer immunotherapy, miRNA-mRNA interactions

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