Document Detail


Downregulation of miR-21 inhibits EGFR pathway and suppresses the growth of human glioblastoma cells independent of PTEN status.
MedLine Citation:
PMID:  20048743     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
MicroRNAs (miRNAs) are a class of endogenous small noncoding RNAs that regulate gene expression after transcription. Aberrant expression of miRNAs has been shown to be involved in tumorigenesis. We showed that miR-21 was one of the most frequently overexpressed miRNA in human glioblastoma (GBM) cell lines. To explore whether miR-21 can serve as a therapeutic target for glioblastoma, we downregulated miR-21 with a specific antisense oligonucleotide and found that apoptosis was induced and cell-cycle progression was inhibited in vitro in U251 (PTEN mutant) and LN229 (PTEN wild-type) GBM cells; xenograft tumors from antisense-treated U251 cells were suppressed in vivo. Antisense-miR-21-treated cells showed a decreased expression of EGFR, activated Akt, cyclin D, and Bcl-2. Although miR-21 is known to regulate PTEN and downregulation of miR-21 led to increased PTEN expression both endogenously and in a reporter gene assay, the GBM suppressor effect of antisense-miR-21 is most likely independent of PTEN regulation because U251 has mutant PTEN. Microarray analysis showed that the knockdown of miR-21 significantly altered expression of 169 genes involved in nine cell-cycle and signaling pathways. Taken together, our studies provide evidence that miR-21 may serve as a novel therapeutic target for malignant gliomas independent of PTEN status.
Authors:
Xuan Zhou; Yu Ren; Lynette Moore; Mei Mei; Yongping You; Peng Xu; Baoli Wang; Guangxiu Wang; Zhifan Jia; Peiyu Pu; Wei Zhang; Chunsheng Kang
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-01-04
Journal Detail:
Title:  Laboratory investigation; a journal of technical methods and pathology     Volume:  90     ISSN:  1530-0307     ISO Abbreviation:  Lab. Invest.     Publication Date:  2010 Feb 
Date Detail:
Created Date:  2010-02-01     Completed Date:  2010-04-09     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0376617     Medline TA:  Lab Invest     Country:  United States    
Other Details:
Languages:  eng     Pagination:  144-55     Citation Subset:  IM    
Affiliation:
Department of Neurosurgery, Tianjin Medical University General Hospital, Laboratory of Neuro-oncology, Tianjin Neurological Institute, Tianjin, China.
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis
Cell Line, Tumor
Cyclin D / metabolism
Down-Regulation*
Female
Gene Expression Profiling
Glioblastoma / metabolism*
Humans
Metabolic Networks and Pathways
Mice
Mice, Nude
MicroRNAs / metabolism*
Neoplasm Transplantation
Oligonucleotide Array Sequence Analysis
Oligonucleotides, Antisense
PTEN Phosphohydrolase / physiology*
Proto-Oncogene Proteins c-akt / metabolism
Proto-Oncogene Proteins c-bcl-2 / metabolism
Receptor, Epidermal Growth Factor / metabolism*
Signal Transduction
Transplantation, Heterologous
Chemical
Reg. No./Substance:
0/Cyclin D; 0/MIRN21 microRNA, human; 0/MicroRNAs; 0/Oligonucleotides, Antisense; 0/Proto-Oncogene Proteins c-bcl-2; EC 2.7.10.1/Receptor, Epidermal Growth Factor; EC 2.7.11.1/Proto-Oncogene Proteins c-akt; EC 3.1.3.48/PTEN protein, human; EC 3.1.3.67/PTEN Phosphohydrolase

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