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Updated: Mar 16, 2026
Global Identification of Co-Translational Interaction Networks by Selective Ribosome Profiling
Published on: October 7, 2021
Identification of rifampin-regulated functional modules and related microRNAs in human hepatocytes based on the
Jin Li1, Ying Wang1,2, Lei Wang1
1College of Automation, Harbin Engineering University, 145 Nantong Street, Nangang District, Harbin, Heilongjiang, 150001, China.
Background:
In combination with gene expression profiles, the protein interaction network (PIN) constructs a dynamic network that includes multiple functional modules. Previous studies have demonstrated that rifampin can influence drug metabolism by regulating drug-metabolizing enzymes, transporters, and microRNAs (miRNAs). Rifampin induces gene expression, at least in part, by activating the pregnane X receptor (PXR), which induces gene expression; however, the impact of rifampin on global gene regulation has not been examined under the molecular network frameworks.
Methods:
In this study, we extracted rifampin-induced significant differentially expressed genes (SDG) based on the gene expression profile. By integrating the SDG and human protein interaction network (HPIN), we constructed the rifampin-regulated protein interaction network (RrPIN). Based on gene expression measurements, we extracted a subnetwork that showed enriched changes in molecular activity. Using the Kyoto Encyclopedia of Genes and Genomes (KEGG), we identified the crucial rifampin-regulated biological pathways and associated genes. In addition, genes targeted by miRNAs that were significantly differentially expressed in the miRNA expression profile were extracted based on the miRNA-gene prediction tools. The miRNA-regulated PIN was further constructed using associated genes and miRNAs. For each miRNA, we further evaluated the potential impact by the gene interaction network using pathway analysis. RESULTS AND DISCCUSSION: We extracted the functional modules, which included 84 genes and 89 interactions, from the RrPIN, and identified 19 key rifampin-response genes that are associated with seven function pathways that include drug response and metabolism, and cancer pathways; many of the pathways were supported by previous studies. In addition, we identified that a set of 6 genes (CAV1, CREBBP, SMAD3, TRAF2, KBKG, and THBS1) functioning as gene hubs in the subnetworks that are regulated by rifampin. It is also suggested that 12 differentially expressed miRNAs were associated with 6 biological pathways.
Conclusions:
Our results suggest that rifampin contributes to changes in the expression of genes by regulating key molecules in the protein interaction networks. This study offers valuable insights into rifampin-induced biological mechanisms at the level of miRNAs, genes and proteins.
Insights
Rifampin alters gene expression by regulating key molecules in protein interaction networks, offering insights into its biological mechanisms at miRNA, gene, and protein levels.
Area of Science:
- Molecular Biology
- Systems Biology
- Pharmacogenomics
Background:
- Rifampin influences drug metabolism via drug-metabolizing enzymes, transporters, and microRNAs (miRNAs).
- Rifampin activates the pregnane X receptor (PXR), inducing gene expression, but its global regulatory impact on molecular networks is underexplored.
Purpose of the Study:
- To construct and analyze the rifampin-regulated protein interaction network (RrPIN).
- To identify key rifampin-response genes, biological pathways, and associated miRNAs.
- To elucidate rifampin's global gene regulatory mechanisms within molecular network frameworks.
Main Methods:
- Integrated significant differentially expressed genes (SDG) with the human protein interaction network (HPIN) to build the RrPIN.
- Utilized Kyoto Encyclopedia of Genes and Genomes (KEGG) for pathway analysis.
- Identified miRNA-targeted genes and constructed miRNA-regulated networks.
Main Results:
- Identified 19 key rifampin-response genes within functional modules, linked to drug response, metabolism, and cancer pathways.
- Discovered 6 hub genes (CAV1, CREBBP, SMAD3, TRAF2, KBKG, THBS1) central to rifampin-regulated subnetworks.
- Associated 12 differentially expressed miRNAs with 6 biological pathways.
Conclusions:
- Rifampin modulates gene expression through key molecules in protein interaction networks.
- Provides comprehensive insights into rifampin's biological effects across miRNA, gene, and protein levels.
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