Glycine decarboxylase (GLDC) has been identified to be dysregulated and plays pivotal roles in various cancers. Besides, studies have suggested that GLDC expression is elevated in oral squamous cell carcinoma (OSCC) and associated with a worse prognosis, but the precise role and molecular mechanism of GLDC in OSCC remain unexplored. The current study first confirmed the high expression of GLDC in OSCC and its correlation with worse survival in patients with OSCC. By knocking down GLDC, it was discovered that the growth and colony formation of OSCC cells, as well as the development of xenograft tumors, were effectively suppressed. In addition, GLDC deficiency inhibited the migration and invasion of OSCC cells in vitro through regulating EMT markers and attenuated lung metastasis in vivo. Mechanistically, GLDC was found to affect the activity of the p53 signaling pathway. GLDC depletion retarded the progression of OSCC by activating the p53 signaling pathway. Moreover, p300 co‐functioned with TFAP2A to induce acetylation of GLDC, which resulted in the upregulation of GLDC in OSCC. To conclude, acetylation‐induced GLDC upregulation facilitated the tumorigenesis and metastasis of OSCC by its inhibition of the activity of the p53 signaling pathway.

中文翻译：

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H3K27 乙酰化激活的 GLDC 通过抑制 p53 信号通路加速口腔鳞状细胞癌的进展


甘氨酸脱羧酶 （GLDC） 已被确定为失调，并在各种癌症中起关键作用。此外，研究表明，GLDC 在口腔鳞状细胞癌 （OSCC） 中的表达升高，并且与较差的预后相关，但 GLDC 在 OSCC 中的确切作用和分子机制仍未得到探索。目前的研究首先证实了 GLDC 在 OSCC 中的高表达及其与 OSCC 患者较差生存率的相关性。通过敲低 GLDC，发现 OSCC 细胞的生长和集落形成以及异种移植肿瘤的发展都得到了有效抑制。此外，GLDC 缺陷通过调节 EMT 标志物和减轻体内肺转移，在体外抑制 OSCC 细胞的迁移和侵袭。从机制上讲，发现 GLDC 会影响 p53 信号通路的活性。GLDC 耗竭通过激活 p53 信号通路延缓 OSCC 的进展。此外，p300 与 TFAP2A 共同发挥作用，诱导 GLDC 乙酰化，从而导致 OSCC 中 GLDC 的上调。总之，乙酰化诱导的 GLDC 上调通过抑制 p53 信号通路的活性促进了 OSCC 的肿瘤发生和转移。