Fan Zhirui, Zheng Yuanyuan, Li Xiaoli, Deng Xiaoming, Ba Yan, Feng Kun, Su Jin, Wang Hui, Suo Zhenhe, Li Lifeng
Department of Chinese and Western Integrative Medicine, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China.
Department of Oncology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China.
Mol Ther Oncolytics. 2022 Feb 14;24:772-787. doi: 10.1016/j.omto.2022.02.005. eCollection 2022 Mar 17.
Pentraxin 3 (PTX3) is an inflammatory molecule that is closely related to the proliferation, invasion, and metastasis of cancer. In order to explore the role of PTX3 in the occurrence and development of esophageal carcinoma (ESCA), we modified the PTX3 gene in ESCA cell lines to obtain the model of gene knockout and overexpression and studied cell proliferation, cycle, apoptosis, migration ability, energy metabolism, and sensitivity to chemotherapy and radiotherapy. We observed the increase in cell proliferation, cycle, apoptosis, migration ability, and sensitivity to chemotherapy and radiotherapy in the PTX3 knockout model, while in the PTX3 overexpression model, these phenomena were significantly reduced. Knockout of the PTX3 also resulted in decreased cell glycolysis and increased oxidative phosphorylation, which is consistent with other findings that PTX3 affects the tumorigenic ability of cells and their sensitivity to docetaxel. In ESCA, SOX9 directly regulates the expression of PTX3, while human leukocyte antigen (HLA)-system-related genes are significantly up-regulated when lacking PTX3. These results indicate that SOX9 may play a crucial role in regulating PTX3 and affecting the HLA system in ESCA.
五聚体蛋白3(PTX3)是一种炎症分子,与癌症的增殖、侵袭和转移密切相关。为了探究PTX3在食管癌(ESCA)发生发展中的作用,我们在ESCA细胞系中对PTX3基因进行修饰,以获得基因敲除和过表达模型,并研究细胞增殖、周期、凋亡、迁移能力、能量代谢以及对化疗和放疗的敏感性。我们观察到在PTX3基因敲除模型中细胞增殖、周期、凋亡、迁移能力以及对化疗和放疗的敏感性增加,而在PTX3过表达模型中,这些现象显著降低。PTX3基因敲除还导致细胞糖酵解减少和氧化磷酸化增加,这与其他研究结果一致,即PTX3影响细胞的致瘤能力及其对多西他赛的敏感性。在ESCA中,SOX9直接调控PTX3的表达,而当缺乏PTX3时,人类白细胞抗原(HLA)系统相关基因显著上调。这些结果表明,SOX9可能在调控PTX3以及影响ESCA中的HLA系统方面发挥关键作用。