Functional network analysis of gene-phenotype connectivity based on pioglitazone
Weihao Wang1, Lina Zhang1, Xiaoxia Wang1
1Department of Endocrinology, Beijing Hospital, National Center of Gerontology, Beijing 100010, P.R. China.
Experimental and Therapeutic Medicine
|December 5, 2019
Summary
Pioglitazone, an anti-hyperglycemic drug, activates PPAR, enhancing insulin sensitivity. This study investigated pioglitazone
Area of Science:
- Pharmacology and Molecular Biology
- Oncology
- Bioinformatics
Background:
- Pioglitazone is an effective anti-hyperglycemic drug that activates peroxisome proliferator-activated receptor (PPAR).
- Pioglitazone's mechanism involves enhancing insulin sensitivity and reducing hepatic glucose production.
- The drug's association with increased bladder cancer risk and its underlying mechanisms remain unclear.
Purpose of the Study:
- To investigate the molecular mechanisms linking pioglitazone to bladder cancer risk.
- To identify potential drug targets and biological pathways affected by pioglitazone.
- To explore the impact of pioglitazone on bladder cancer patient survival through genetic alterations.
Main Methods:
- Utilized the Drug-Target Interactome (DTome) database to identify pioglitazone's direct target proteins (DTPs) and associated genes.
- Performed enrichment analysis on DTP-associated genes using Cytoscape software.
- Conducted functional network analysis and Kaplan-Meier analysis to assess genetic alterations and survival rates.
Main Results:
- Identified 4 direct target proteins and associated genes for pioglitazone.
- Discovered 12 Kyoto Encyclopedia of Genes and Genomes pathways, including 'PPAR signaling pathway' and 'pathways in cancer'.
- Found that pioglitazone may influence bladder cancer patient survival via genetic alterations in target genes.
Conclusions:
- Pioglitazone's molecular targets and affected pathways suggest a link to cancer pathways.
- Genetic alterations in pioglitazone's target genes may impact bladder cancer patient survival.
- Pioglitazone should be used with caution due to potential associations with bladder cancer risk and survival outcomes.
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