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CASZ1 induces skeletal muscle and rhabdomyosarcoma differentiation through a feed-forward loop with MYOD and MYOG

Author

Listed:
  • Zhihui Liu

    (Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute)

  • Xiyuan Zhang

    (Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute)

  • Haiyan Lei

    (Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute)

  • Norris Lam

    (Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute)

  • Sakereh Carter

    (Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute)

  • Oliver Yockey

    (Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute)

  • Max Xu

    (Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute)

  • Arnulfo Mendoza

    (Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute)

  • Edjay R. Hernandez

    (Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute)

  • Jun S. Wei

    (Genetics Branch, Center for Cancer Research, National Cancer Institute)

  • Javed Khan

    (Genetics Branch, Center for Cancer Research, National Cancer Institute)

  • Marielle E. Yohe

    (Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute)

  • Jack F. Shern

    (Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute)

  • Carol J. Thiele

    (Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute)

Abstract

Embryonal rhabdomyosarcoma (ERMS) is a childhood cancer that expresses myogenic master regulatory factor MYOD but fails to differentiate. Here, we show that the zinc finger transcription factor CASZ1 up-regulates MYOD signature genes and induces skeletal muscle differentiation in normal myoblasts and ERMS. The oncogenic activation of the RAS-MEK pathway suppresses CASZ1 expression in ERMS. ChIP-seq, ATAC-seq and RNA-seq experiments reveal that CASZ1 directly up-regulates skeletal muscle genes and represses non-muscle genes through affecting regional epigenetic modifications, chromatin accessibility and super-enhancer establishment. Next generation sequencing of primary RMS tumors identified a single nucleotide variant in the CASZ1 coding region that potentially contributes to ERMS tumorigenesis. Taken together, loss of CASZ1 activity, due to RAS-MEK signaling or genetic alteration, impairs ERMS differentiation, contributing to RMS tumorigenesis.

Suggested Citation

  • Zhihui Liu & Xiyuan Zhang & Haiyan Lei & Norris Lam & Sakereh Carter & Oliver Yockey & Max Xu & Arnulfo Mendoza & Edjay R. Hernandez & Jun S. Wei & Javed Khan & Marielle E. Yohe & Jack F. Shern & Caro, 2020. "CASZ1 induces skeletal muscle and rhabdomyosarcoma differentiation through a feed-forward loop with MYOD and MYOG," Nature Communications, Nature, vol. 11(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-14684-4
    DOI: 10.1038/s41467-020-14684-4
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    Cited by:

    1. Deblina Banerjee & Sukriti Bagchi & Zhihui Liu & Hsien-Chao Chou & Man Xu & Ming Sun & Sara Aloisi & Zalman Vaksman & Sharon J. Diskin & Mark Zimmerman & Javed Khan & Berkley Gryder & Carol J. Thiele, 2024. "Lineage specific transcription factor waves reprogram neuroblastoma from self-renewal to differentiation," Nature Communications, Nature, vol. 15(1), pages 1-18, December.

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