| dc.description.abstract | Myogenic regulatory factors (MRFs), including Myf5, MyoD, Myogenin and MRF4, are essential for skeletal muscle (SKM) lineage determination and differentiation. Basic Fibroblast Growth Factor (bFGF) is commonly used for culturing myogenic stem cells (MuSC, or satellite cells) but is known to activate Myf5 while inhibiting MyoD expression. In terminal-stage cancers, serious SKM wasting (cachexia) occurs, and MyoD expression is similarly repressed while Myf5 expression is upregulated by cachexia signals. Our lab has confirmed that recombinant GST-bFGF and C26 cell-conditioned medium (C26M) inhibit both myogenesis and MyoD expression in C2C12 cells. However, this inhibition is less pronounced in satellite cells as compared to C2C12 cells, necessitating further investigation into the reasons for this difference. Also, MyoD mRNA stability is increased by bFGF in both growth medium (GM) and differentiation medium (DM), as well as by cachexia signals, suggesting a complex regulatory mechanism affecting MyoD expression at multiple levels. Moreover, various MyoD cis-elements have been identified as targets of bFGF signaling at different myogenic stages. Multiple MyoD cis-elements are also targeted by C26M. Additionally, the Myf5 promoter is repressed by bFGF and C26M signals, which presents a discrepancy between promoter activity and mRNA level that needs further investigation. Furthermore, CREeRNA, a non-coding RNA transcribed from CRE and critical for MyoD epigenetic activation, is repressed by bFGF. However, overexpression of CREeRNA does not rescue the bFGF-repressed MyoD mRNA expression in GM. Additionally, Myf5 promoter activity is repressed by bFGF and C26M, which is opposite to the transcriptional expression. Thus, the mechanism needs to be further investigated. Currently, efforts are focused on identifying the transcription factors mediating the repressive effects of bFGF and C26M on MyoD expression. Understanding these mechanisms will provide deeper insights into the regulation of MyoD and potential therapeutic strategies for muscle-wasting conditions associated with cancer cachexia. | en_US |