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Integrative network analysis of rifampin-regulated miRNAs and their functions in human hepatocytes

Jin Li1, Ying Wang1,2, Lei Wang1

  • 1College of Automation, Harbin Engineering University, 145 Nantong Street, Nangang District, Harbin, Heilongjiang, 150001, China.

Bio-Medical Materials and Engineering
|September 26, 2015
PubMed

Insights

Rifampin, a tuberculosis drug, affects how the body processes other medications. This study identifies specific microRNAs (miRNAs) and genes involved in rifampin

Area of Science:

  • Pharmacology
  • Molecular Biology
  • Genomics

Background:

  • Rifampin is a crucial tuberculosis treatment that enhances drug metabolism in human hepatocytes.
  • Rifampin's indirect influence on drug disposition involves microRNA (miRNA), PXR, and gene regulation.
  • The precise roles of miRNAs in rifampin-induced drug disposition remain incompletely understood.

Purpose of the Study:

  • To identify significantly differentially expressed miRNAs (SDEM) associated with rifampin.
  • To predict miRNA-regulated co-expression target genes (MCeTG) and construct a miRNA-regulated co-expressed protein interaction network (MCePIN).
  • To elucidate the functional implications of these miRNA-gene interactions in response to rifampin.

Main Methods:

  • Extraction and analysis of significantly differentially expressed miRNAs (SDEM) from rifampin-treated samples.
  • Prediction of miRNA-regulated co-expression target genes (MCeTG).
  • Construction of a miRNA-regulated co-expressed protein interaction network (MCePIN) and functional enrichment analysis (GO, KEGG).

Main Results:

  • Identified 20 SDEM and predicted 632 miRNA-regulated genes.
  • Constructed an MCePIN revealing 10 miRNAs and 33 genes linked to 7 key functions.
  • These functions include response to wounding, wound healing, response to drug, defense response, inflammatory response, liver development, and drug metabolism.

Conclusions:

  • This study provides novel insights into the molecular mechanisms underlying rifampin's effects on miRNA, gene, and protein expression.
  • The identified miRNAs and genes are crucial for understanding rifampin-induced alterations in drug disposition and related biological processes.
  • Findings contribute to a deeper comprehension of drug metabolism regulation by miRNAs in the context of rifampin therapy.
Keywords:
P450PPI networkRifampingenehepatocytemiRNA

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