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PFKFB3 通过细胞焦亡和糖酵解进程调控卵巢癌细胞的生长和迁移。

PFKFB3 Regulates the Growth and Migration of Ovarian Cancer Cells through Pyroptosis and Warburg Effect Progression.

机构信息

Department of Obstetrics and Gynecology, Wuhan No. 1 Hospital, Wuhan 430030, China.

Wuhan No.1 Hospital.

出版信息

J Environ Pathol Toxicol Oncol. 2024;43(4):53-64. doi: 10.1615/JEnvironPatholToxicolOncol.2024052948.

DOI:10.1615/JEnvironPatholToxicolOncol.2024052948
PMID:39016141
Abstract

Ovarian cancer is one of the most common malignant tumors in female reproductive organs. Its incidence rate is second only to uterine body cancer and cervical cancer, posing a serious threat to women's health. Herein, we explored that PFKFB3 in cancer progression of ovarian cancer and its underlying mechanism. All the serum samples from ovarian cancer were collected by our hospital. PFKFB3 mRNA expressions in patients with ovarian cancer and ovarian cancer cell lines were up-regulated. PFKFB3 protein expressions in ovarian cancer cells were induced. ovarian cancer patients with high PFKFB3expression had lower survival rate. The PFKFB3gene promoted cell proliferation and EDU cells, and increased cell metastasis of ovarian cancer. Si-PFKFB3 reduced cell proliferation and EDU cells, and decreased cell metastasis of ovarian cancer. PFKFB3 gene up-regulation reduced caspase-3/9 activity levels of ovarian cancer. Si-PFKFB3 also promoted caspase-3/9 activity levels of ovarian cancer. PFKFB3 gene promoted Warburg effect progression of ovarian cancer. PFKFB3 gene reduced NLRP3-induced pyroptosis of ovarian cancer. PFKFB3 suppressed NLRP3 expression. NLRP3 was one target spot for PFKFB3 on pyroptosis of ovarian cancer. Taken together, we conclude that PFKFB3 suppressed NLRP3 axis to reduce pyroptosis and increase Warburg effect progression of ovarian cancer, and provide molecular insight into the mechanisms by which the PFKFB3 regulates pyroptosis of ovarian cancer.

摘要

卵巢癌是女性生殖器官最常见的恶性肿瘤之一,其发病率仅次于子宫体癌和宫颈癌,严重威胁着妇女的健康。在此,我们探讨了 PFKFB3 在卵巢癌进展中的作用及其潜在机制。我们医院收集了所有卵巢癌患者的血清样本。卵巢癌患者和卵巢癌细胞系中 PFKFB3mRNA 的表达上调。PFKFB3 蛋白在卵巢癌细胞中被诱导表达。PFKFB3 高表达的卵巢癌患者的生存率较低。PFKFB3 基因促进卵巢癌细胞的增殖和 EDU 细胞,并增加细胞转移。Si-PFKFB3 减少卵巢癌细胞的增殖和 EDU 细胞,并减少细胞转移。PFKFB3 基因上调降低了卵巢癌细胞中 caspase-3/9 的活性水平。Si-PFKFB3 也促进了卵巢癌细胞中 caspase-3/9 的活性水平。PFKFB3 基因促进了卵巢癌的瓦博格效应进展。PFKFB3 基因降低了 NLRP3 诱导的卵巢癌细胞焦亡。PFKFB3 抑制 NLRP3 的表达。NLRP3 是 PFKFB3 对卵巢癌细胞焦亡的一个靶点。综上所述,我们得出结论,PFKFB3 通过抑制 NLRP3 轴来减少卵巢癌的焦亡和增加瓦博格效应的进展,为 PFKFB3 调节卵巢癌焦亡的机制提供了分子见解。

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