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Cited by 15MicroRNA in disease regulationMacrophage Migration Inhibitory FactorCellular Mechanics and Interactions

Impaired cell migration and structural defects in myeloid cells overexpressing miR-30b and miR-142-3p

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Valverde, Araceli, Nares, Salvador, Naqvi, Afsar Raza·2020·Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
DOI 10.1016/j.bbagrm.2020.194628PMC PMC7686300
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Abstract

Macrophages (MΦ) and dendritic cells (DC) play a fundamental role in shaping immune responses by sensing a plethora of Pathogen Associated Molecular Patterns (PAMPs), phagocytosis and antigen presentation to T lymphocytes. These important biological processes require efficient cell movement and an intact cellular morphology for dynamic interaction. The role of microRNAs (miRs) in this regard, however, is not well understood. In the present study, we show that miR-30b and miR-142-3p regulate migration and morphology of MΦ and DC. Transient overexpression of miR-30b and miR-142-3p attenuates migration and these cells display unique morphological deformities observed under electron microscopy. In addition, miR-142-3p overexpression in MΦ impaired phagocytosis of FITC-conjugated latex beads using live microscopy imaging. Interestingly, live cell imaging and F-actin staining revealed marked changes in the cell polarity and actin polymerization status, respectively. To identify miR-142-3p regulated pathways, we profiled global transcriptome changes in miR-142-3p or control mimic transfected DC. Expression of several genes were differentially altered by miR-142-3p and were associated with pathways related to cell movement, cell adhesion, and cytoskeletal rearrangement. Bioinformatics analysis identified a significant subset of downregulated genes with one or more predicted miR-142-3p binding sites in their 3'UTR strongly suggesting direct post-transcriptional impact of these miRNAs on multiple transcripts. Using dual luciferase assays, novel miR-142-3p binding sites were validated for three genes (Vinculin, Dab2 and Skap2) directly associated with cytoskeletal rearrangement and cell movement. In summary, our results show that miR-30b and miR-142-3p are regulators of myeloid cell cytoskeletal homeostasis and morphology.

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  • miR-142-3p targets Vinculin, Dab2, and Skap2, which are directly associated with cytoskeletal rearrangement and cell movement.

    “Valverde et al. identified miR-142-3p as microRNA targeting three genes (Vinculin, Dab2 and Skap2) directly associated with cytoskeletal rearrangement and cell movement [129].”

    From MicroRNAs as Regulators of Phagocytosis (2022) · cites this paper as [129]

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Sorted by citations

Authors
Valverde, A., Nares, S., & Naqvi, A. R.
Affiliations
University of Illinois Chicago (US)
Corresponding author
Naqvi, Afsar Raza
ORCID
Venue
Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
Publisher
Elsevier BV
Published
2020-11
Volume
1863
Issue
11
Pages
194628
ISSN
1874-9399 (ISSN-L)
DOI
10.1016/j.bbagrm.2020.194628
PMC
PMC7686300
OpenAlex
W3089269625
Cited by
15
References
1
Citations by year
2026: 2 · 2024: 3 · 2023: 5 · 2022: 3 · 2021: 1 · 2020: 1
FWCI
0.86
Type
journal article
Language
en
Open access
Licence
Locations
  • Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institutes of Health
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
  • Life Sciences › Immunology and Microbiology › Immunology › Macrophage Migration Inhibitory Factor
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
Keywords
miR-30b, miR-142-3p, microRNA, macrophages, dendritic cells, myeloid cell migration, cell morphology, phagocytosis, actin polymerization, cell polarity, cytoskeletal rearrangement, 3' UTR binding sites, post-transcriptional regulation, vinculin, Dab2, SKAP2, gene expression profiling
MeSH terms
Cell Differentiation, Cell Line, Cell Movement, Cytoskeleton, Gene Expression Regulation, Homeostasis, Humans, Models, Biological, Monocytes, Phagocytosis, Signal Transduction, Gene Expression, Genes, Reporter, Myeloid Cells, RNA Interference, MicroRNAs, Transcriptome

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