Date of Award
12-1-2025
Degree Name
Master of Science
Department
Molecular Biology Microbiology and Biochemistry
First Advisor
Davie, Judy
Abstract
Rhabdomyosarcoma (RMS) is an aggressive pediatric cancer arising from skeletal muscle precursor cells. This thesis investigates the role of the ISWI chromatin remodeler subunit SMARCA1 in normal myogenesis and RMS pathogenesis. Overexpression of SMARCA1 in C2C12 cells inhibits the expression of myogenic markers (Myod1, Myog, Lmod1, Acta1, Tnni2) and impairs myotube formation, as assessed by immunostaining for myosin heavy chain. These effects are partially rescued by Wnt signaling activation using 10 mM LiCl treatment. Conversely, SMARCA1 is upregulated in RMS cell lines (RH30, RH28, RD, RD2) compared to C2C12 cells. CRISPR-Cas9-mediated knockout of SMARCA1 in RH30 cells leads to a significant downregulation of TGF-β pathway components (TGFBR1), EMT-related genes (SNAIL1, WNT11, KRAS, MRAS, TCF7L1) as demonstrated by RT-qPCR. Also, a slight downregulation of HDAC2 protein expression, and downregulation of MYOD1 and MYOG were observed by Western blot. These findings suggest that SMARCA1 acts as a regulator of muscle differentiation and plays a critical role in maintaining the expression of genes involved in TGF-β signaling and EMT in RMS cells, highlighting its potential as a therapeutic target.
Access
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