Proto-oncogenes in a eukaryotic unicellular organism play essential roles in plasmodial growth in host cells

BMC Genomics. 2018 Dec 6;19(1):881. doi: 10.1186/s12864-018-5307-4.

Abstract

Background: The eukaryotic unicellular protist Plasmodiophora brassicae is an endocellular parasite of cruciferous plants. In host cortical cells, this protist develops a unicellular structure that is termed the plasmodium. The plasmodium is actually a multinucleated cell, which subsequently splits and forms resting spores. The mechanism for the growth of this endocellular parasite in host cell is unclear.

Results: Here, combining de novo genome sequence and transcriptome analysis of strain ZJ-1, we identified top five significant enriched KEGG pathways of differentially expressed genes (DEGs), namely translation, cell growth and death, cell communication, cell motility and cancers. We detected 171 proto-oncogenes from the genome of P. brassicae that were implicated in cancer-related pathways, of which 46 were differential expression genes. Three predicted proto-oncogenes (Pb-Raf1, Pb-Raf2, and Pb-MYB), which showed homology to the human proto-oncogenes Raf and MYB, were specifically activated during the plasmodial growth in host cortical cells, demonstrating their involvement in the multinucleate development stage of the unicellular protist organism. Gene networks involved in the tumorigenic-related signaling transduction pathways and the activation of 12 core genes were identified. Inhibition of phosphoinositol-3-kinase relieved the clubroot symptom and significantly suppressed the development process of plasmodia.

Conclusions: Proto-oncogene-related regulatory mechanisms play an important role in the plasmodial growth of P. brassicae.

Keywords: Brassica napus; Cancer; Clubroot; Plasmodiophora brassicae; Proto-oncogenes; Tumor.

MeSH terms

  • Amino Acid Sequence
  • Brassica napus / metabolism
  • Brassica napus / parasitology
  • Gene Expression Profiling
  • Genes, myb / genetics
  • Genome, Protozoan*
  • Humans
  • Imidazoles / pharmacology
  • Imidazoles / therapeutic use
  • Oxazepines / pharmacology
  • Oxazepines / therapeutic use
  • Plant Diseases / parasitology
  • Plant Diseases / therapy
  • Plant Roots / cytology
  • Plant Roots / metabolism
  • Plant Roots / parasitology
  • Plasmodiophorida / genetics*
  • Plasmodiophorida / growth & development
  • Proto-Oncogene Mas
  • Proto-Oncogenes / genetics*
  • Sequence Alignment
  • Spores, Protozoan / drug effects
  • Spores, Protozoan / genetics
  • Transcriptome / drug effects
  • raf Kinases / genetics

Substances

  • 2-(3-(2-(1-isopropyl-3-methyl-1H-1,2-4-triazol-5-yl)-5,6-dihydrobenzo(f)imidazo(1,2-d)(1,4)oxazepin-9-yl)-1H-pyrazol-1-yl)-2-methylpropanamide
  • Imidazoles
  • MAS1 protein, human
  • Oxazepines
  • Proto-Oncogene Mas
  • raf Kinases