Unraveling the distinct role of MICAL2 in skeletal muscle physiology and rhabdomyosarcoma tumor progression

MICAL2, a protein implicated in cancer progression, has emerged as a potential therapeutic target due to its role in modulating cellular behaviors, including proliferation and migration. However, its involvement in RMS pathogenesis and therapeutic potential remains unclear.

In this study, we investigated the role of MICAL2 in RMS progression using in vitro and in vivo models, revealing elevated MICAL2 expression in RMS cell lines compared to healthy counterparts. Knockdown (KD) of MICAL2 using plasmid constructs resulted in reduced proliferation and migration of RMS cells and a significant decrease in metabolic activity in MICAL2-silenced RMS cells was demonstrated. Moreover, in vivo experiments using a TET-ON cassette for silencing MICAL2 in tumor-bearing mice showed that MICAL2 knockdown attenuated primary tumor growth and inhibited metastasis formation, as confirmed by bioluminescence imaging and histological analyses, while also improving ambulation performance.