Mitochondrial properties in Rhabdomyosarcoma: An insight into the molecular mechanisms of muscle differentiation

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Rhabdomyosarcoma (RMS) is a type of cancer that arises in muscle tissue and primarily affects children. RMS cells remain immature and thus, their lack of differentiation into mature muscle cells is one of the hallmarks of this disease. The cause of this lack of differentiation remains unknown. In this study, we hope to gain an insight into the molecular mechanisms of RMS cell differentiation and how mitochondrial properties may be involved in this process, particularly related to mitochondrial movement, morphology and protein markers of mitochondrial biogenesis. For the purpose of this study, human skeletal muscle cells (HSKM) and rhabdomyosarcoma (RD) were induced to differentiate for a period of 7 days. While no difference was observed in mitochondrial speed, acceleration and distance travelled from the origin in HSKM cells after 7 days of differentiation, RD cells exhibited an approximate 2‐ fold increase in speed and acceleration after 7 days of differentiation. Moreover, mitochondria in RD cells had a more punctate appearance after 7 days of differentiation. p53, a regulator of cell cycle arrest, was markedly elevated in RD cells. However, BAX, a regulator of apoptosis, remained highly expressed in HSMK cells throughout the 7 day differentiation period. While these changes occurred in HSMK and RD cells, no difference in PGC1‐α, a marker of mitochondrial biogenesis, was observed. This study suggests that mitochondrial properties and motility are altered in RD cells when induced to differentiate, and this could be related to the degree of tumorigenesis. Supported by NSERC and Mitacs.