Abstract
A previous study showed that miR-221/222 can regulate cell apoptosis. p53 is a well known tumor suppressor which can influence the chemosensitivity of glioma cells. However, the effect of miR-221/222 in gliomas with different p53 status is unknown. Here, we demostrate that knockdown of miR-221/222 increases apoptosis in human gliomas of different p53 types (U251 cells, p53 mutant-type; LN308 cells, p53 null-type; and U87 cells, p53 wild-type). Furthermore, the effect of miR-221/22 caused no change of p53 expression in the glioma cells studied. In addition, when a specific siRNA against p53 was employed in U87 cells, no attenuation of apoptosis was found after knockdown of miR-221/222. Importantly, we found that As-miR-221/222-treated cells increased expression of Bax, cytochrome c, Apaf-1 and cleaved-caspase-3. Our results showed that low expression of miR-221/222 sensitized glioma cells to temozolomide (TMZ); in addition, ectopic expression of PUMA by pcDNA-PUMA had a similar effect. Taken together, our study indicates that downregulated miR-221/222 can sensitize glioma cells to TMZ by regulating apoptosis independently of p53 status.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Apoptosis / drug effects
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Apoptosis / genetics*
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Apoptosis Regulatory Proteins / genetics
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Apoptosis Regulatory Proteins / metabolism
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Apoptotic Protease-Activating Factor 1 / genetics
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Apoptotic Protease-Activating Factor 1 / metabolism
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Brain Neoplasms / genetics
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Brain Neoplasms / metabolism
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Caspase 3 / genetics
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Caspase 3 / metabolism
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Cytochromes c / genetics
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Cytochromes c / metabolism
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Dacarbazine / analogs & derivatives*
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Dacarbazine / pharmacology
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Down-Regulation / drug effects
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Gene Knockdown Techniques / methods
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Glioma / drug therapy
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Glioma / genetics*
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Glioma / metabolism
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Humans
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MicroRNAs / genetics*
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MicroRNAs / metabolism
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Mitochondria / genetics
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Mitochondria / metabolism
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins / metabolism
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RNA, Small Interfering / genetics
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Signal Transduction / genetics
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Temozolomide
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Tumor Cells, Cultured
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Tumor Suppressor Protein p53 / genetics*
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Tumor Suppressor Protein p53 / metabolism
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bcl-2-Associated X Protein / genetics
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bcl-2-Associated X Protein / metabolism
Substances
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APAF1 protein, human
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Apoptosis Regulatory Proteins
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Apoptotic Protease-Activating Factor 1
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BBC3 protein, human
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MIRN221 microRNA, human
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MIRN222 microRNA, human
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MicroRNAs
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Proto-Oncogene Proteins
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RNA, Small Interfering
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TP53 protein, human
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Tumor Suppressor Protein p53
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bcl-2-Associated X Protein
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Dacarbazine
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Cytochromes c
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Caspase 3
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Temozolomide