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Effects of AEBP1 knockdown on gene expression profiles in human skeletal muscle myoblasts

ABSTRACT: We recently identified adipocyte enhancer binding protein 1 (AEBP1) as a novel cancer stroma-associated gene and reported that AEBP1 activates cancer-associated fibroblasts in oral cancer. In this study, we show that AEBP1 is negatively associated with skeletal muscle cell differentiation. We found that AEBP1 is downregulated during the diffraction of human skeletal muscle myoblasts (HSMMs). Microarray analysis revealed that knockdown of AEBP1 significantly upregulated a number of genes associated with myogenesis in HSMMs. Notably, co-culture of HSMMs with oral squamous cell carcinoma cells resulted in downregulation of muscle-related genes and upregulation of AEBP1 in HSMMs.

ORGANISM(S): Homo sapiens

PROVIDER: GSE268740 | GEO | 2024/11/14

REPOSITORIES: GEO

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Project description:The majority of cell surface and secreted proteins are modified by glycans and this glycosylation process plays an important role in the development of multicellular organisms. These glycan modifications enable communication between cells and the extracellular matrix via interactions with specific glycan-binding lectins and the regulation of receptor-mediated signalling. Glycosylation plays an important role in myogenesis and the development of muscle tissue but our molecular understanding of the precise glycans, catalytic enzymes and lectins involved remain only partially understood. Here, we quantified dynamic remodeling of the membrane-associated proteome during in vitro myogenesis. We observed wide-spread changes in the abundance of several receptors and important enzymes regulating glycosylation. Quantification of released N-linked glycans via glycomic analysis confirmed remodeling of the glycome with a switch in sialic acid linkages, and changes in di-galactosylation and paucimannosylation. Quantitative glycoproteomic analysis with stable isotope labelling, enrichment of glycopeptides and analysis via multiple fragmentation approaches identified precise glycoproteins containing these regulated glycans including integrins and growth factor receptors. Myogenesis was also associated with the regulation of several lectins including the up-regulation of Galectin-1 (LGALS1). CRISPR/Cas9-mediated deletion of Lgals1 inhibited differentiation and myotube formation suggesting an early defect in the myogenic program. We also observed similar changes in N-glycosylation and the up-regulation of LGALS1 during postnatal skeletal muscle development in mice. Finally, treatment of new-born mice with recombinant adeno-associated viruses to express LGALS1 in the musculature resulted in enhanced muscle mass. Our data will be a valuable resource to further understand the role of glycosylation and lectins on myogenesis and may aid in the development of intervention strategies aimed at promoting healthy muscle.

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Effects of AEBP1 knockdown on gene expression profiles in human skeletal muscle myoblasts

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