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

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

Nature communications (2020-02-16)
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, Carol J Thiele
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
MISSION® esiRNA, targeting mouse Casz1
Sigma-Aldrich
MISSION® esiRNA, targeting human CASZ1
Sigma-Aldrich
MISSION® esiRNA, targeting human MYOG
Sigma-Aldrich
MISSION® pLKO.1-puro Non-Mammalian shRNA Control Transduction Particles, Targets no known mammalian genes
Sigma-Aldrich
MISSION® esiRNA, targeting human MAP2K1
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MISSION® esiRNA, targeting human MYF5
Sigma-Aldrich
Anti-MyoD1 Antibody, clone 5.2F, Chemicon®, from mouse
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Anti-Myogenin Antibody, Chemicon®, from mouse
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Anti-trimethyl-Histone H3 (Lys27) Antibody, Upstate®, from rabbit