Scientific Reports (Nov 2024)

AEBP1 is a negative regulator of skeletal muscle cell differentiation in oral squamous cell carcinoma

  • Fumika Okazaki,
  • Akira Yorozu,
  • Shohei Sekiguchi,
  • Takeshi Niinuma,
  • Reo Maruyama,
  • Hiroshi Kitajima,
  • Eiichiro Yamamoto,
  • Kazuya Ishiguro,
  • Mutsumi Toyota,
  • Yui Hatanaka,
  • Koyo Nishiyama,
  • Kazuhiro Ogi,
  • Masahiro Kai,
  • Kenichi Takano,
  • Shingo Ichimiya,
  • Akihiro Miyazaki,
  • Hiromu Suzuki

DOI
https://doi.org/10.1038/s41598-024-79061-3
Journal volume & issue
Vol. 14, no. 1
pp. 1 – 11

Abstract

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Abstract The tumor microenvironment plays a pivotal role in cancer development. We recently reported that in oral squamous cell carcinoma (OSCC), adipocyte enhancer-binding protein 1 (AEBP1) is abundantly expressed in cancer-associated fibroblasts (CAFs), leading to CAF activation and inhibition of CD8 + T cell infiltration. In the present study, we investigated whether AEBP1 contributes to the destruction and atrophy of muscle tissues in OSCC. By analyzing human skeletal muscle myoblasts (HSMMs), we found that AEBP1 is downregulated during muscle cell differentiation. Transcriptome analysis revealed that AEBP1 knockdown significantly upregulates myogenesis-related genes in HSMMs, and qRT-PCR and western blot analyses confirmed the induction of muscle-related genes, including MYOG, in HSMMs after AEBP1 knockdown. Conversely, ectopic expression of AEBP1 strongly suppressed myogenesis-related genes in HSMMs. Notably, indirect co-culture of HSMMs with OSCC cells led to AEBP1 upregulation and robust suppression of muscle-related genes in HSMMs. Treatment with TGF-β1 also upregulated AEBP1 and suppressed expression of muscle-related genes in HSMMs. Our findings suggest that AEBP1 is a negative regulator of skeletal muscle cell differentiation and that OSCC cells inhibit muscle cell differentiation, at least in part, by inducing AEBP1.

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