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MicroRNA 452 Regulates Cell Proliferation, Cell Migration, and Angiogenesis in Colorectal Cancer by Suppressing VEGFA Expression

The human microRNA 452 (MIR452) was identified as a colorectal cancer (CRC)-associated micro RNA (miRNA) by miRNA expression profiling of human CRC tissues versus normal colorectal tissues. It was significantly up-regulated in human CRC tissues. However, the functional mechanisms of MIR452 and its t...

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Autores principales: Mo, Ji Su, Park, Won Cheol, Choi, Suck-Chei, Yun, Ki Jung, Chae, Soo-Cheon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6826374/
https://www.ncbi.nlm.nih.gov/pubmed/31652600
http://dx.doi.org/10.3390/cancers11101613
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author Mo, Ji Su
Park, Won Cheol
Choi, Suck-Chei
Yun, Ki Jung
Chae, Soo-Cheon
author_facet Mo, Ji Su
Park, Won Cheol
Choi, Suck-Chei
Yun, Ki Jung
Chae, Soo-Cheon
author_sort Mo, Ji Su
collection PubMed
description The human microRNA 452 (MIR452) was identified as a colorectal cancer (CRC)-associated micro RNA (miRNA) by miRNA expression profiling of human CRC tissues versus normal colorectal tissues. It was significantly up-regulated in human CRC tissues. However, the functional mechanisms of MIR452 and its target genes in CRC remain unclear. We identified 27 putative MIR452 target genes, and found that the vascular endothelial growth factor A (VEGFA) was a direct target gene of MIR452. Both cellular and extracellular VEGFA levels were significantly downregulated in CRC cells upon their transfection with MIR452 or siVEGFA. VEGFA expression was frequently downregulated in human CRC tissues in comparison with that in their healthy counterparts. We showed that MIR452 regulated the expression of genes in the VEGFA-mediated signal transduction pathways vascular endothelial growth factor receptor 1 (VEGFR2)–mitogen-activated protein kinase (MAPK) and VEGFR2–SRC proto-oncogene non-receptor tyrosine kinase (SRC) in CRC cells. Immunohistological analyses of xenografted MIR452-overexpressing CRC cells in mice showed that MIR452 regulated cell proliferation and angiogenesis. Furthermore, aortic ring angiogenesis assay in rats clearly showed that the number of microvessels formed was significantly reduced by MIR452 transfection. Our findings suggest that MIR452 regulates cell proliferation, cell migration, and angiogenesis by suppressing VEGFA expression in early CRC progression; therefore, MIR452 may have therapeutic value in relation to human CRC.
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spelling pubmed-68263742019-11-18 MicroRNA 452 Regulates Cell Proliferation, Cell Migration, and Angiogenesis in Colorectal Cancer by Suppressing VEGFA Expression Mo, Ji Su Park, Won Cheol Choi, Suck-Chei Yun, Ki Jung Chae, Soo-Cheon Cancers (Basel) Article The human microRNA 452 (MIR452) was identified as a colorectal cancer (CRC)-associated micro RNA (miRNA) by miRNA expression profiling of human CRC tissues versus normal colorectal tissues. It was significantly up-regulated in human CRC tissues. However, the functional mechanisms of MIR452 and its target genes in CRC remain unclear. We identified 27 putative MIR452 target genes, and found that the vascular endothelial growth factor A (VEGFA) was a direct target gene of MIR452. Both cellular and extracellular VEGFA levels were significantly downregulated in CRC cells upon their transfection with MIR452 or siVEGFA. VEGFA expression was frequently downregulated in human CRC tissues in comparison with that in their healthy counterparts. We showed that MIR452 regulated the expression of genes in the VEGFA-mediated signal transduction pathways vascular endothelial growth factor receptor 1 (VEGFR2)–mitogen-activated protein kinase (MAPK) and VEGFR2–SRC proto-oncogene non-receptor tyrosine kinase (SRC) in CRC cells. Immunohistological analyses of xenografted MIR452-overexpressing CRC cells in mice showed that MIR452 regulated cell proliferation and angiogenesis. Furthermore, aortic ring angiogenesis assay in rats clearly showed that the number of microvessels formed was significantly reduced by MIR452 transfection. Our findings suggest that MIR452 regulates cell proliferation, cell migration, and angiogenesis by suppressing VEGFA expression in early CRC progression; therefore, MIR452 may have therapeutic value in relation to human CRC. MDPI 2019-10-22 /pmc/articles/PMC6826374/ /pubmed/31652600 http://dx.doi.org/10.3390/cancers11101613 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Mo, Ji Su
Park, Won Cheol
Choi, Suck-Chei
Yun, Ki Jung
Chae, Soo-Cheon
MicroRNA 452 Regulates Cell Proliferation, Cell Migration, and Angiogenesis in Colorectal Cancer by Suppressing VEGFA Expression
title MicroRNA 452 Regulates Cell Proliferation, Cell Migration, and Angiogenesis in Colorectal Cancer by Suppressing VEGFA Expression
title_full MicroRNA 452 Regulates Cell Proliferation, Cell Migration, and Angiogenesis in Colorectal Cancer by Suppressing VEGFA Expression
title_fullStr MicroRNA 452 Regulates Cell Proliferation, Cell Migration, and Angiogenesis in Colorectal Cancer by Suppressing VEGFA Expression
title_full_unstemmed MicroRNA 452 Regulates Cell Proliferation, Cell Migration, and Angiogenesis in Colorectal Cancer by Suppressing VEGFA Expression
title_short MicroRNA 452 Regulates Cell Proliferation, Cell Migration, and Angiogenesis in Colorectal Cancer by Suppressing VEGFA Expression
title_sort microrna 452 regulates cell proliferation, cell migration, and angiogenesis in colorectal cancer by suppressing vegfa expression
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6826374/
https://www.ncbi.nlm.nih.gov/pubmed/31652600
http://dx.doi.org/10.3390/cancers11101613
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