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Pax3 loss of function delays tumour progression in kRAS-induced zebrafish rhabdomyosarcoma models.
- Source :
-
Scientific reports [Sci Rep] 2022 Oct 13; Vol. 12 (1), pp. 17149. Date of Electronic Publication: 2022 Oct 13. - Publication Year :
- 2022
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Abstract
- 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.<br /> (© 2022. The Author(s).)
- Subjects :
- 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
Zebrafish genetics
Zebrafish metabolism
Zebrafish Proteins metabolism
Rhabdomyosarcoma genetics
Rhabdomyosarcoma pathology
Rhabdomyosarcoma, Embryonal genetics
Subjects
Details
- Language :
- English
- ISSN :
- 2045-2322
- Volume :
- 12
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Scientific reports
- Publication Type :
- Academic Journal
- Accession number :
- 36229514
- Full Text :
- https://doi.org/10.1038/s41598-022-21525-5