| MicroRNA-195 plays a tumor-suppressor role in human glioblastoma cells by targeting signaling pathways involved in cellular proliferation and invasion. | |
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MedLine Citation:
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PMID: 22217655 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Accumulating evidence has implicated the deregluation of miRNAs in tumorigenesis. Previous studies have reported that microRNA-195 (miR-195) is markedly down-regulated in human glioblastoma cells, compared with normal brain tissue, but the biological role of miR-195 in glioblastoma development is currently unknown. In this study, we define a tumor-suppressor role for miR-195 in human glioblastoma cells. Over-expression of miR-195 in glioblastoma cell lines robustly arrested cell cycle progression and significantly repressed cellular invasion. We identified E2F3 and CCND3 as functional downstream targets of miR-195 in glioblastoma cells. Through knockdown studies, we demonstrated that E2F3 was the dominant effector of miR-195-mediated cell cycle arrest and that CCND3 was a key mediator of miR-195-induced inhibition of glioblastoma cell invasion. Furthermore, we showed that p27(Kip1) was an important regulator downstream of CCND3 and that the accumulation of p27(Kip1) in the cytoplasm might be responsible for the miR-195-mediated cell invasion inhibition in glioblastoma cells. This work provides evidence for the initial mechanism by which miR-195 negatively regulates both the proliferation and invasion of glioblastoma cells, suggesting that the down-regulation of miR-195 might contribute to the malignant transformation of glioblastoma cells and could be a molecular signature associated with glioblastoma progression. |
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Authors:
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Qian-Qian Zhang; Hui Xu; Mian-Bo Huang; Li-Ming Ma; Qiao-Juan Huang; Qing Yao; Hui Zhou; Liang-Hu Qu |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2012-01-04 |
Journal Detail:
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Title: Neuro-oncology Volume: 14 ISSN: 1523-5866 ISO Abbreviation: Neuro-oncology Publication Date: 2012 Mar |
Date Detail:
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Created Date: 2012-02-20 Completed Date: 2012-06-12 Revised Date: 2013-03-04 |
Medline Journal Info:
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Nlm Unique ID: 100887420 Medline TA: Neuro Oncol Country: England |
Other Details:
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Languages: eng Pagination: 278-87 Citation Subset: IM |
Affiliation:
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Corresponding Author: Liang-Hu Qu, Sun Yat-Sen University, 135 Xingangxi Road, Guangzhou 510275, PR China. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Brain Neoplasms
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genetics*,
pathology Cell Cycle Checkpoints / genetics* Cell Line, Tumor Cell Proliferation Down-Regulation Gene Knockdown Techniques Genes, Tumor Suppressor Glioblastoma / genetics*, metabolism, pathology Humans MicroRNAs / genetics, metabolism* Neoplasm Invasiveness Signal Transduction / physiology Up-Regulation |
| Chemical | |
Reg. No./Substance:
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0/MIRN195 microRNA, human; 0/MicroRNAs |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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