期刊
JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY
卷 64, 期 2, 页码 138-148出版社
SAGE PUBLICATIONS LTD
DOI: 10.1369/0022155415623515
关键词
MiR-21; glioblastoma; glioma; angiogenesis; cancer stem cell; in situ hybridization
类别
资金
- Region of Southern Denmark
- Research Council for Health and Disease
- Ministry of Higher Education and Science
- grant of Else and Aage Gronbaek-Olsen
- Foundation of Merchant M. Kristian Kjaer and wife Margrethe Kjaer born la Cour-Holmen
- grant of fmr. Dir. Leo Nielsen and wife Karen Margrethe Nielsen for medical basic research
- Beckett Foundation, Research Foundation of University of Southern Denmark
- Foundation of Fam. Hede Nielsen
- Foundation of Margot and John Friberg
- Foundation of Dir. Jacob Madsen and wife Olga
MicroRNA-21 (miR-21) is the most consistently over-expressed microRNA (miRNA) in malignant gliomas. We have previously reported that miR-21 is upregulated in glioma vessels and subsets of glioma cells. To better understand the role of miR-21 in glioma angiogenesis and to characterize miR-21-positive tumor cells, we systematically stained consecutive serial sections from ten astrocytomas for miR-21, hypoxia-inducible factor-1 alpha (HIF-1 alpha), vascular endothelial growth factor (VEGF), phosphatase and tensin homolog (PTEN), octamer-binding transcription factor 4 (Oct4), sex-determining region Y box 2 (Sox2) and CD133. We developed an image analysis-based co-localization approach allowing global alignment and quantitation of the individual markers, and measured the miR-21 in situ hybridization signal against the immunohistochemical staining of the six different markers. miR-21 significantly co-localized with the hypoxia-and angiogenesis-associated markers HIF-1 alpha (p=0.0020) and VEGF (p=0.0096), whereas the putative miR-21 target, PTEN, was expressed independently of miR-21. Expression of stem cell markers Oct4, Sox2 and CD133 was not associated with miR-21. In six glioblastoma cultures, miR-21 did not correlate with the six markers. These findings suggest that miR-21 is linked to glioma angiogenesis, that miR-21 is unlikely to regulate PTEN, and that miR-21-positive tumor cells do not possess stem cell characteristics.
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