The DOI matches its Crossref record; 64 of the 65 references it cites were found in a registry or an index.
MicroRNA-21 Targets Sprouty2 and Promotes Cellular Outgrowths
Open accessAbstract
The posttranscriptional regulator, microRNA-21 (miR-21), is up-regulated in many forms of cancer, as well as during cardiac hypertrophic growth. To understand its role, we overexpressed it in cardiocytes where it revealed a unique type of cell-to-cell “linker” in the form of long slender outgrowths and branches. We subsequently confirmed that miR-21 directly targets and down-regulates the expression of Sprouty2 (SPRY2), an inhibitor of branching morphogenesis and neurite outgrowths. We found that β-adrenergic receptor (βAR) stimulation induces up-regulation of miR-21 and down-regulation of SPRY2 and is, likewise, associated with connecting cell branches. Knockdown of SPRY2 reproduced the branching morphology in cardiocytes, and vice versa, knockdown of miR-21 using a specific ‘miRNA eraser’ or overexpression of SPRY2 inhibited βAR-induced cellular outgrowths. These structures enclose sarcomeres and connect adjacent cardiocytes through functional gap junctions. To determine how this aspect of miR-21 function translates in cancer cells, we knocked it down in colon cancer SW480 cells. This resulted in disappearance of their microvillus-like protrusions accompanied by SPRY2-dependent inhibition of cell migration. Thus, we propose that an increase in miR-21 enhances the formation of various types of cellular protrusions through directly targeting and down-regulating SPRY2.
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“MiR-21 targets SPRY2 in cardiomyocytes and SW480 colon cancer cells, enhancing cell migration (Sayed et al., 2008).”
From Modulation of K-Ras-Dependent Lung Tumorigenesis by MicroRNA-21 (2010) · cites this paper as Sayed et al., 2008
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Sorted by citations
MicroRNA-21 contributes to myocardial disease by stimulating MAP kinase signalling in fibroblasts
Thum, T., Gross, C., Fiedler, J., Fischer, T., Kissler, S., Bussen, M., Galuppo, P., Just, S., Rottbauer, W., Frantz, S., et al. (2008) · Nature · doi:10.1038/nature07511 · Cited by 2,349
MicroRNAs in Development and Disease
Sayed, D. H., & Abdellatif, M. (2011) · Physiological Reviews · doi:10.1152/physrev.00006.2010 · Cited by 1,101
Self-citationmiR‐21: a small multi‐faceted RNA
Krichevsky, A. M., & Gabriely, G. (2009) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2008.00556.x · Cited by 987
MicroRNA as Biomarkers and Diagnostics
Wang, J., Chen, J., & Sen, S. (2016) · Journal of Cellular Physiology · doi:10.1002/jcp.25056 · Cited by 793
MicroRNA sponges: Progress and possibilities
Ebert, M. S., & Sharp, P. A. (2010) · RNA · doi:10.1261/rna.2414110 · Cited by 762
Metadata
- Authors
- Sayed, D., Rane, S., Lypowy, J., He, M., Chen, I.-Y., Vashistha, H., Yan, L., Malhotra, A., Vatner, D., & Abdellatif, M.
- Affiliations
- Cardiovascular Institute Hospital (JP)
- University of Medicine and Dentistry of New Jersey (US)
- Venue
- Molecular Biology of the Cell
- Published
- 2008-08
- Volume
- 19
- Issue
- 8
- Pages
- 3272-3282
- ISSN
- 1059-1524 (ISSN-L)
- 1939-4586
- PMC
- PMC2488276
- OpenAlex
- W2160447597
- Cited by
- 355
- References
- 65
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 4 · 2023: 3 · 2022: 7 · 2021: 5 · 2020: 17 · 2019: 9 · 2018: 9 · 2017: 15 · 2016: 22 · 2015: 32 · 2014: 41 · 2013: 38 · 2012: 29
- FWCI
- 13.10
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular Biology of the Cell (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Rutgers University Community Repository (Rutgers University) (submittedVersion)
- Funders
- National Institutes of Health
- National Heart, Lung, and Blood Institute (R01HL081381, R01HL057970)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Congenital heart defects research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- miR-21, Sprouty2, cardiomyocytes, beta-adrenergic signaling, cell protrusions, gap junctions, cardiac hypertrophy, colon cancer, cell migration, neurite outgrowth, branching morphogenesis, post-transcriptional regulation
- MeSH terms
- Animals, Cell Communication, Cell Movement, Colonic Neoplasms, Male, Membrane Proteins, Mice, Inbred C57BL, Receptors, Adrenergic, beta, RNA Processing, Post-Transcriptional, Subcellular Fractions, Down-Regulation, Protein Serine-Threonine Kinases, Gap Junctions, MicroRNAs, Intracellular Signaling Peptides and Proteins, Adaptor Proteins, Signal Transducing, Cell Proliferation, Mice
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