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AEBP1 是口腔鳞状细胞癌中骨骼肌细胞分化的负调控因子。

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

机构信息

Department of Molecular Biology, Sapporo Medical University School of Medicine, S1, W17, Chuo-ku, Sapporo, 060-8556, Japan.

Department of Oral Surgery, Sapporo Medical University School of Medicine, Sapporo, Japan.

出版信息

Sci Rep. 2024 Nov 9;14(1):27425. doi: 10.1038/s41598-024-79061-3.

DOI:10.1038/s41598-024-79061-3
PMID:39521917
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11550323/
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.

摘要

肿瘤微环境在癌症发展中起着关键作用。我们最近报道，在口腔鳞状细胞癌（OSCC）中，脂肪细胞增强结合蛋白 1（AEBP1）在癌相关成纤维细胞（CAFs）中大量表达，导致 CAF 激活并抑制 CD8+T 细胞浸润。在本研究中，我们研究了 AEBP1 是否有助于 OSCC 中肌肉组织的破坏和萎缩。通过分析人类骨骼肌成肌细胞（HSMMs），我们发现 AEBP1 在肌肉细胞分化过程中下调。转录组分析显示，AEBP1 敲低显著上调 HSMMs 中的成肌相关基因，qRT-PCR 和 Western blot 分析证实 AEBP1 敲低后 HSMMs 中肌肉相关基因 MYOG 的诱导。相反，AEBP1 的异位表达强烈抑制 HSMMs 中的成肌相关基因。值得注意的是，HSMMs 与 OSCC 细胞的间接共培养导致 AEBP1 上调和 HSMMs 中肌肉相关基因的强烈抑制。TGF-β1 的处理也上调了 AEBP1 并抑制了 HSMMs 中肌肉相关基因的表达。我们的研究结果表明，AEBP1 是骨骼肌细胞分化的负调节剂，并且 OSCC 细胞至少部分通过诱导 AEBP1 来抑制肌肉细胞分化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae8f/11550323/1137b9369cb4/41598_2024_79061_Fig7_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae8f/11550323/1137b9369cb4/41598_2024_79061_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae8f/11550323/bc3e84ab25eb/41598_2024_79061_Fig1_HTML.jpg
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ACLP Activates Cancer-Associated Fibroblasts and Inhibits CD8+ T-Cell Infiltration in Oral Squamous Cell Carcinoma.ACLP激活口腔鳞状细胞癌中的癌症相关成纤维细胞并抑制CD8 + T细胞浸润。
Cancers (Basel). 2023 Aug 28;15(17):4303. doi: 10.3390/cancers15174303.
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CXCL12 is expressed by skeletal muscle cells in tongue oral squamous cell carcinoma.
CXCL12 由舌口腔鳞状细胞癌中的骨骼肌细胞表达。
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