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Induction of apoptosis through ER stress and TP53 in MCF-7 cells by the nanoparticle [Gd@C-82(OH)(22)](n): A systems biology study
Wang, L; Meng, J; Cao, WP; Li, QZ; Qiu, YQ; Sun, BY; Li, LM;孙宝云
2014
发表期刊METHODS
卷号67期号:3页码:394-406
摘要The nanoparticle gadolinium endohedral metallofullerenol [Gd@C-82(OH)(22)](n) is a new candidate for cancer treatment with low toxicity. However, its anti-cancer mechanisms remain mostly unknown. In this study, we took a systems biology view of the gene expression profiles of human breast cancer cells (MCF-7) and human umbilical vein endothelial cells (ECV304) treated with and without [Gd@C-82(OH)(22)](n), respectively, measured by the Agilent Gene Chip G4112F. To properly analyze these data, we modified a suit of statistical methods we developed. For the first time we applied the sub-sub normalization to Agilent two-color microarrays. Instead of a simple linear regression, we proposed to use a one-knot SPLINE model in the sub-sub normalization to account for nonlinear spatial effects. The parameters estimated by least trimmed squares- and S-estimators show similar normalization results. We made several kinds of inferences by integrating the expression profiles with the bioinformatic knowledge in KEGG pathways, Gene Ontology, JASPAR, and TRANSFAC. In the transcriptional inference, we proposed the BASE2.0 method to infer a transcription factor's up-regulation and down-regulation activities separately. Overall, [Gd@C-82(OH)(22)](n) induces more differentiation in MCF-7 cells than in ECV304 cells, particularly in the reduction of protein processing such as protein glucosylation, folding, targeting, exporting, and transporting. Among the KEGG pathways, the ErbB signaling pathway is up-regulated, whereas protein processing in endoplasmic reticulum (ER) is down-regulated. CHOP, a key pro-apoptotic gene downstream of the ER stress pathway, increases to nine folds in MCF-7 cells after treatment. These findings indicate that ER stress may be one important factor that induces apoptosis in MCF-7 cells after [Gd@C-82(OH)(22)](n) treatnment. The expression profiles of genes associated with ER stress and apoptosis are statistically consistent with other profiles reported in the literature, such as those of HEK293T and MCF-7 cells induced by the miR-23a similar to 27a similar to 24-2 cluster. Furthermore, one of the inferred regulatory mechanisms comprises the apoptosis network centered around TP53, whose effective regulation of apoptosis is somehow reestablished after [Gd@C-82(OH)(22)](n) treatment. These results elucidate the application and development of [Gd@C-82(OH)(22)](n) and other fullerene derivates. (C) 2014 Elsevier Inc. All rights reserved.
关键词Nanoparticle Microarray normalization Transcriptional inference Apoptosis ER stress TP53
学科领域Biochemistry & Molecular Biology
DOI10.1016/j.ymeth.2014.01.007
收录类别SCI
WOS记录号WOS:000336883500016
引用统计
被引频次:7[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.ihep.ac.cn/handle/311005/225183
专题多学科研究中心
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GB/T 7714
Wang, L,Meng, J,Cao, WP,et al. Induction of apoptosis through ER stress and TP53 in MCF-7 cells by the nanoparticle [Gd@C-82(OH)(22)](n): A systems biology study[J]. METHODS,2014,67(3):394-406.
APA Wang, L.,Meng, J.,Cao, WP.,Li, QZ.,Qiu, YQ.,...&Li, LM;孙宝云.(2014).Induction of apoptosis through ER stress and TP53 in MCF-7 cells by the nanoparticle [Gd@C-82(OH)(22)](n): A systems biology study.METHODS,67(3),394-406.
MLA Wang, L,et al."Induction of apoptosis through ER stress and TP53 in MCF-7 cells by the nanoparticle [Gd@C-82(OH)(22)](n): A systems biology study".METHODS 67.3(2014):394-406.
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