H3K27 Acetylation-Activated GLDC Accelerated the Advancement of Oral Squamous Cell Carcinoma by Suppressing the p53 Signaling Pathway.

IF 4.4 3区医学 Q2 ENVIRONMENTAL SCIENCES

Environmental Toxicology Pub Date : 2024-10-17 DOI:10.1002/tox.24379

Chen Xu,Qingfeng Xu,Haibing Yang

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引用次数: 0

Abstract

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.

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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发展

甘氨酸脱羧酶（Glycine decarboxylase，GLDC）已被发现在多种癌症中失调并发挥关键作用。此外，有研究表明，GLDC在口腔鳞状细胞癌（OSCC）中表达升高，并与预后恶化相关，但GLDC在OSCC中的确切作用和分子机制仍有待探索。本研究首次证实了GLDC在OSCC中的高表达及其与OSCC患者生存率降低的相关性。研究发现，通过敲除GLDC，OSCC细胞的生长和集落形成以及异种移植肿瘤的发生均被有效抑制。此外，GLDC的缺乏还通过调节EMT标记物抑制了体外OSCC细胞的迁移和侵袭，并减轻了体内的肺转移。从机理上讲，GLDC会影响p53信号通路的活性。通过激活p53信号通路，GLDC耗竭可延缓OSCC的进展。此外，p300与TFAP2A共同作用诱导GLDC乙酰化，从而导致GLDC在OSCC中上调。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。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Environmental Toxicology 环境科学-毒理学

CiteScore

7.10

自引率

8.90%

发文量

261

审稿时长

4.5 months

期刊介绍： The journal publishes in the areas of toxicity and toxicology of environmental pollutants in air, dust, sediment, soil and water, and natural toxins in the environment.Of particular interest are: Toxic or biologically disruptive impacts of anthropogenic chemicals such as pharmaceuticals, industrial organics, agricultural chemicals, and by-products such as chlorinated compounds from water disinfection and waste incineration; Natural toxins and their impacts; Biotransformation and metabolism of toxigenic compounds, food chains for toxin accumulation or biodegradation; Assays of toxicity, endocrine disruption, mutagenicity, carcinogenicity, ecosystem impact and health hazard; Environmental and public health risk assessment, environmental guidelines, environmental policy for toxicants.