Functional network analysis of gene-phenotype connectivity based on pioglitazone
Functional network analysis of gene-phenotype connectivity based on pioglitazone
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基于吡格列酮的基因-表型连接功能网络分析
DOI：
10.3892/etm.2019.8162
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发表时间：
2019-11
期刊：
影响因子：
--
通讯作者：
Lixin Guo
中科院分区：
文献类型：
--
作者：
Weihao Wang;Lina Zhang;Xiaoxia Wang;Dong Lin;Qi Pan;Lixin Guo
吡格列酮是一种胰岛素增敏剂，是一种有效的抗高血糖药物。吡格列酮的作用机制是通过激活过氧化物酶体增殖物激活受体（PPAR），导致外周组织和肝脏的胰岛素敏感性增强，导致肝糖的产生和输出减少。据报道，吡格列酮会增加膀胱癌的风险，但其潜在机制仍不清楚。据推测，可以通过系统分析药物公布的数据来预测吡格列酮活性的调节。这一假设通过查询药物靶标相互作用组 (DTome) 进行了测试，这是一种基于网络的工具，提供来自三个数据库（DrugBank、PharmGSK 和蛋白质相互作用网络分析）的开源数据。共鉴定出吡格列酮的 4 个直接靶蛋白 (DTP) 和其他 DTP 相关基因。随后，使用 Cytoscape 软件对所有 DTP 相关基因进行富集分析。京都基因和基因组百科全书总共鉴定了 12 条通路，包括“PPAR 信号通路”以及“癌症通路”作为相关通路。功能网络分析能够识别吡格列酮的直接和间接靶基因，从而根据已发表的数据库列出可能的生物学功能。此外，Kaplan-Meier分析表明，吡格列酮可能通过靶基因的基因改变（错义突变、截短突变、扩增、深度缺失和融合）影响膀胱癌患者的生存率。因此，应谨慎使用。
Pioglitazone, a type of insulin sensitizer, serves as an effective anti-hyperglycemic drug. The mechanism of action of pioglitazone is through the activation of the peroxisome proliferator-activated receptor (PPAR), which results in enhanced insulin sensitivity of peripheral tissues and the liver, causing a reduction in the production and output of liver sugar. It has been reported that pioglitazone increases the risk of bladder cancer, but the underlying mechanisms have remained elusive. It was hypothesized that modulation of pioglitazone activity may be predicted by systematically analyzing data published on drugs. This hypothesis was tested by querying the Drug-Target Interactome (DTome), a web-based tool that provides open-source data from three databases (DrugBank, PharmGSK and Protein Interaction Network analysis). A total of 4 direct target proteins (DTPs) and further DTP-associated genes were identified for pioglitazone. Subsequently, an enrichment analysis was performed for all DTP-associated genes using Cytoscape software. A total of 12 Kyoto Encyclopedia of Genes and Genomes pathways were identified, including the ‘PPAR signaling pathway’ as well as ‘pathways in cancer’ as relevant pathways. Functional network analysis was able to identify direct and indirect target genes of pioglitazone, resulting in a list of possible biological functions based on published databases. Furthermore, Kaplan-Meier analysis indicated that pioglitazone may affect the survival rate of patients with bladder cancer through genetic alterations (missense mutation, truncating mutation, amplification, deep deletion and fusion) of target genes. Therefore, it should be used with caution.
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影响因子：
7.3
作者：
Gao J;Aksoy BA;Dogrusoz U;Dresdner G;Gross B;Sumer SO;Sun Y;Jacobsen A;Sinha R;Larsson E;Cerami E;Sander C;Schultz N
通讯作者：
Schultz N
影响因子：
7.7
作者：
Halstead AM;Kapadia CD;Bolzenius J;Chu CE;Schriefer A;Wartman LD;Bowman GR;Arora VK
通讯作者：
Arora VK
DOI：
10.1093/ajhp/56.17.1698
发表时间：
1999-09
期刊：
American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists
影响因子：
--
作者：
J. Miller
通讯作者：
J. Miller
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
30.8
作者：
Al-Ahmadie HA;Iyer G;Lee BH;Scott SN;Mehra R;Bagrodia A;Jordan EJ;Gao SP;Ramirez R;Cha EK;Desai NB;Zabor EC;Ostrovnaya I;Gopalan A;Chen YB;Fine SW;Tickoo SK;Gandhi A;Hreiki J;Viale A;Arcila ME;Dalbagni G;Rosenberg JE;Bochner BH;Bajorin DF;Berger MF;Reuter VE;Taylor BS;Solit DB
通讯作者：
Solit DB