Pax3 loss of function delays tumour progression in kRAS-induced zebrafish rhabdomyosarcoma models

Sci Rep. 2022 Oct 13;12(1):17149. doi: 10.1038/s41598-022-21525-5.


Rhabdomyosarcoma is a soft tissue cancer that arises in skeletal muscle due to mutations in myogenic progenitors that lead to ineffective differentiation and malignant transformation. The transcription factors Pax3 and Pax7 and their downstream target genes are tightly linked with the fusion positive alveolar subtype, whereas the RAS pathway is usually involved in the embryonal, fusion negative variant. Here, we analyse the role of Pax3 in a fusion negative context, by linking alterations in gene expression in pax3a/pax3b double mutant zebrafish with tumour progression in kRAS-induced rhabdomyosarcoma tumours. Several genes in the RAS/MAPK signalling pathway were significantly down-regulated in pax3a/pax3b double mutant zebrafish. Progression of rhabdomyosarcoma tumours was also delayed in the pax3a/pax3b double mutant zebrafish indicating that Pax3 transcription factors have an unappreciated role in mediating malignancy in fusion negative rhabdomyosarcoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Forkhead Box Protein O1 / metabolism
  • Forkhead Transcription Factors / metabolism
  • Oncogene Proteins, Fusion / genetics
  • PAX3 Transcription Factor / genetics
  • PAX3 Transcription Factor / metabolism
  • PAX7 Transcription Factor / genetics
  • PAX7 Transcription Factor / metabolism
  • Paired Box Transcription Factors / genetics
  • Paired Box Transcription Factors / metabolism
  • Proto-Oncogene Proteins p21(ras) / genetics
  • Proto-Oncogene Proteins p21(ras) / metabolism
  • Rhabdomyosarcoma* / genetics
  • Rhabdomyosarcoma* / pathology
  • Rhabdomyosarcoma, Embryonal* / genetics
  • Zebrafish / genetics
  • Zebrafish / metabolism
  • Zebrafish Proteins / metabolism


  • Forkhead Box Protein O1
  • Forkhead Transcription Factors
  • Oncogene Proteins, Fusion
  • PAX3 Transcription Factor
  • PAX7 Transcription Factor
  • Paired Box Transcription Factors
  • Zebrafish Proteins
  • Kras protein, zebrafish
  • Proto-Oncogene Proteins p21(ras)