title: Downregulation of miR-221/222 sensitizes glioma cells to temozolomide             by regulating apoptosis independently of p53 status.
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.
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, PR China.
authors.forename: Lingchao
authors.initials: L
authors.lastname: Chen
authors.forename: Junxia
authors.initials: J
authors.lastname: Zhang
authors.forename: Lei
authors.initials: L
authors.lastname: Han
authors.forename: Anling
authors.initials: A
authors.lastname: Zhang
authors.forename: Chunzhi
authors.initials: C
authors.lastname: Zhang
authors.forename: Yongri
authors.initials: Y
authors.lastname: Zheng
authors.forename: Tao
authors.initials: T
authors.lastname: Jiang
authors.forename: Peiyu
authors.initials: P
authors.lastname: Pu
authors.forename: Chuanlu
authors.initials: C
authors.lastname: Jiang
authors.forename: Chunsheng
authors.initials: C
authors.lastname: Kang
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000235:genetics*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D053477:Apoptotic Protease-Activating Factor 1 / Q000235:genetics / Q000378:metabolism; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D045304:Cytochromes c / Q000235:genetics / Q000378:metabolism; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects; D055785:Gene Knockdown Techniques / Q000379:methods; D005910:Glioma / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D000077204:Temozolomide; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; D053477:Apoptotic Protease-Activating Factor 1; D053148:Caspase 3; D045304:Cytochromes c; D003606:Dacarbazine; D035683:MicroRNAs; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; D000077204:Temozolomide; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; C506592:APAF1 protein, human; C438378:BBC3 protein, human; C525709:MIR221, human; C525710:MIR222, human; C495901:TP53 protein, human