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Circular RNA Vav3 sponges gga-miR-375 to promote epithelial-mesenchymal transition

Xinheng Zhang1,2,3,4, Yiming Yan1,2,3, Wencheng Lin1,2,3,4

  • 1a College of Animal Science , South China Agricultural University , Guangzhou , P. R. China.

RNA Biology
|January 5, 2019
PubMed

Insights

Circular RNAs (circRNAs) act as sponges for microRNAs (miRNAs). This study identifies circ-Vav3 as a sponge for gga-miR-375, revealing a circ-Vav3/gga-miR-375/YAP1 axis that promotes tumorigenesis in chickens.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Circular RNAs (circRNAs) are emerging as key regulators in various biological processes, including cancer.
  • MicroRNAs (miRNAs) play crucial roles in gene regulation, and their dysregulation is implicated in tumorigenesis.
  • Avian leukosis virus subgroup J (ALV-J) infection causes liver tumors in chickens, but the underlying molecular mechanisms are not fully understood.

Purpose of the Study:

  • To investigate the role of circRNAs in ALV-J-induced chicken liver tumorigenesis.
  • To identify circRNAs that interact with the downregulated gga-miR-375 in chicken liver tumors.
  • To elucidate the molecular mechanism of circ-Vav3 in regulating tumor development.

Main Methods:

  • circRNA sequencing to identify differentially expressed circRNAs.
  • RNA immunoprecipitation (RIP), biotinylated RNA pull-down, and RNA-fluorescence in situ hybridization (RNA-FISH) to confirm circRNA-miRNA interaction.
  • Dual luciferase reporter assay to validate miRNA target genes.
  • Analysis of epithelial-mesenchymal transition (EMT) markers.
  • Detection of core gene expression in clinical tumor samples.

Main Results:

  • circ-Vav3 was significantly upregulated in ALV-J-induced chicken liver tumors.
  • circ-Vav3 directly interacted with and acted as a sponge for gga-miR-375.
  • YAP1 was identified as a direct target gene of gga-miR-375.
  • The circ-Vav3/gga-miR-375/YAP1 axis promoted EMT and tumorigenesis by regulating EMT markers.
  • Core gene expression levels in clinical samples supported the proposed tumorigenic mechanism.

Conclusions:

  • circ-Vav3 functions as a molecular sponge for gga-miR-375 in chicken liver tumors.
  • The circ-Vav3/gga-miR-375/YAP1 axis is a novel regulator of tumorigenesis induced by ALV-J.
  • This axis promotes EMT and tumor development, offering potential therapeutic targets.
Keywords:
ALV-JEMTYAP1circ-Vav3gga-miR-375

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