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Describing a Transcription Factor Dependent Regulation of the MicroRNA Transcriptome
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Microcystin-LR-regulated transcriptome dynamics in ZFL cells.

Xing Lu1, Juan Tian1, Hua Wen1

  • 1Key Laboratory of Freshwater Biodiversity Conservation and Utilization of Ministry of Agriculture, Yangtze River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Wuhan 430223, Hubei, China.

Aquatic Toxicology (Amsterdam, Netherlands)
|May 29, 2019
PubMed
Summary
This summary is machine-generated.

Microcystin-LR (MC-LR) is a potent toxin affecting aquatic life and human health. This study reveals MC-LR

Keywords:
Gene transcriptionMicrocystinSignaling pathwayTranscriptomeZFL cell line

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Area of Science:

  • Environmental Toxicology
  • Molecular Biology
  • Genomics

Background:

  • Microcystin-LR (MC-LR) is a significant hepatotoxin impacting aquatic ecosystems and human health.
  • Zebrafish liver cell line (ZFL) is a crucial model for toxicological and metabolic studies.
  • The specific toxicity and transcriptional impact of MC-LR on ZFL cells require detailed characterization.

Purpose of the Study:

  • To determine the toxicity of MC-LR in ZFL cells.
  • To investigate the time-dependent effects of MC-LR on the ZFL cell transcriptome.
  • To identify key molecular pathways and regulatory networks affected by MC-LR exposure.

Main Methods:

  • Zebrafish liver cell line (ZFL) toxicity assay to determine EC50.
  • RNA-sequencing analysis of ZFL cells exposed to MC-LR over a 24-hour period.
  • Bioinformatic analysis including differential gene expression, alternative splicing, pathway enrichment, and gene regulatory network construction.

Main Results:

  • The EC50 of MC-LR for ZFL cells was determined to be 80.123 μg/mL.
  • MC-LR exposure regulated 10,209 genes, with significant numbers of both up- and down-regulated genes over time.
  • 1543 genes exhibited differential splicing, with 620 not identified as differentially expressed, highlighting complex transcriptional responses.
  • Mitogen-activated protein kinase (MAPK) and forkhead box O (FoxO) signaling pathways were prominently activated.
  • Steroid biosynthesis and terpenoid backbone biosynthesis pathways were enriched among down-regulated genes.

Conclusions:

  • MC-LR exhibits significant toxicity to ZFL cells, with dose-dependent and time-dependent effects on gene transcription and splicing.
  • The study elucidates the molecular mechanisms underlying MC-LR toxicity, identifying key signaling pathways and regulatory networks.
  • These findings provide valuable insights into the transcriptome dynamics of ZFL cells responding to MC-LR, crucial for understanding its environmental and health impacts.