Cited by 355MicroRNA in disease regulationCongenital heart defects researchDevelopmental Biology and Gene Regulation

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MicroRNA-21 Targets Sprouty2 and Promotes Cellular Outgrowths

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Sayed, Danish, Rane, Shweta, Lypowy, Jacqueline, He, Minzhen, Chen, Ieng-Yi, Vashistha, Himanshu, Yan, Lin, Malhotra, Ashwani, Vatner, Dorothy, Abdellatif, Maha·2008·Molecular Biology of the Cell

DOI 10.1091/mbc.e08-02-0159PMC PMC2488276

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Abstract

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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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)
ORCID: Sayed, Danish
Rane, Shweta
Vashistha, Himanshu
Yan, Lin
Vatner, Dorothy
Abdellatif, Maha
Venue: Molecular Biology of the Cell
Publisher: American Society for Cell Biology (ASCB)
Published: 2008-08
Volume: 19
Issue: 8
Pages: 3272-3282
ISSN: 1059-1524 (ISSN-L)
1939-4586
DOI: 10.1091/mbc.e08-02-0159
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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MicroRNA-21 Targets Sprouty2 and Promotes Cellular Outgrowths

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