Differential expression of miR16 in glioblastoma and glioblastoma stem cells: their correlation with proliferation, differentiation, metastasis and prognosis
| Autor: | Min Ding, Jie He, Rui Tian, Hong Yan, Z Gui, Jing Wu, Qiu-Yan Xu, Jia Yu Wang, Xiao-Hong Zhan |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Male Cancer Research Cellular differentiation Mice Cyclin D1 U87 Child Oncogene Proteins biology Brain Neoplasms Brain Cell Differentiation Middle Aged Prognosis Gene Expression Regulation Neoplastic Survival Rate Proto-Oncogene Proteins c-bcl-2 Neoplastic Stem Cells Female Original Article Stem cell SOXD Transcription Factors Adult Adolescent Mice Nude 03 medical and health sciences Young Adult Cell Line Tumor Cyclin E Genetics Biomarkers Tumor Animals Humans Molecular Biology Aged Cell Proliferation Matrigel Cell growth Cyclin-Dependent Kinase 6 Molecular biology Xenograft Model Antitumor Assays MicroRNAs 030104 developmental biology Cell culture Case-Control Studies biology.protein Cyclin-dependent kinase 6 Glioblastoma |
| Zdroj: | Oncogene |
| ISSN: | 1476-5594 |
| Popis: | The function of miR16 in multiforme glioblastoma multiforme (GBM) and its stem cells (GSCs) remains elusive. To this end, we investigated the patterns of miR16 expression in these cells and their correlation with malignant behaviors and clinical outcomes. The levels of miR16 and its targeted genes in tumor tissue of GBM and GBM SGH44, U87, U251 cells as well as their stem cell counterparts were measured by qRT-PCR or western blot or immunohistochemistry. Luciferase reporter assay was used to confirm the binding of miR16 to 3'-UTR of its target genes. The effects of miR16 on malignant behaviors were investigated, including tumor cell viability, soft-agar colony formation, GSCs Matrigel colony forming and migration and invasion as well as nude mice xenograft model. Differentially expression patterns of miR16 in glioblastoma cells and GSCs cells were found in this study. Changes of miR16 targeted genes, Bcl2 (B cell lymphoma 2), CDK6 (Cyclin-dependent kinase 6), CCND1 (cyclin D1), CCNE1 (cyclin E1) and SOX5 were confirmed in glioblastoma cell lines and tissue specimens. In vitro and in vivo studies showed that tumor cell proliferation was inhibited by miR16 mimic, but enhanced by miR16 inhibitor. The expression level of miR16 positively correlates with GSCs differentiation, but negatively with the abilities of migration, motility, invasion and colony formation in glioblastoma cells. The inhibitory effects of miR16 on its target genes were also found in nude mice xenograft model. Our findings revealed that the miR16 functions as a tumor suppressor in GSCs and its association with prognosis in GBM. |
| Databáze: | OpenAIRE |
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