4.7 Article

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

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SCIENTIFIC REPORTS
卷 12, 期 1, 页码 -

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NATURE PORTFOLIO
DOI: 10.1038/s41598-022-21525-5

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  1. Swedish Cancer Society [20 0827 Pjf]
  2. Cancerforskningsfonden i Norrland [LP 22-2312]
  3. Swedish Research Council [2018-05973]

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By analyzing gene expression changes in pax3a/pax3b double mutant zebrafish, we found that PAX3 transcription factors play an important role in the malignant transformation of fusion negative rhabdomyosarcoma. Specifically, PAX3 transcription factors regulate several key genes in the RAS/MAPK signaling pathway.
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.

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