雌激素/雌激素受体通过增强 hMOF 的表达促进子宫内膜癌细胞的增殖。
Estrogen/estrogen receptor promotes the proliferation of endometrial carcinoma cells by enhancing hMOF expression.
机构信息
Department of Obstetrics and Gynecology, Shengjing Hospital Affiliated to China Medical University, Shenyang, Liaoning, China.
Department of Gynecology, Liaoning Cancer Hospital & Institute, Shenyang, Liaoning, China.
出版信息
Jpn J Clin Oncol. 2020 Mar 9;50(3):241-253. doi: 10.1093/jjco/hyz174.
BACKGROUND
This study aims to analyse the expression of human MOF in endometrial carcinoma cells and its relationship with estrogen and estrogen receptor and to investigate the effect of estrogen-human MOF on the malignant biological behaviours of endometrial carcinoma cells.
METHODS
The expression of human MOF was detected in different endometrial tissues by immunohistochemistry. The effects of human MOF, human MOF combined with estrogen stimulation and estrogen plus anti-human MOF antibody blocking on the proliferation of endometrial carcinoma cells were evaluated by western blotting, real-time polymerase chain reaction, cell proliferation assay and cell cycle distribution. Bioinformatics was used to identify the correlations of human MOF and estrogen and involved pathways.
RESULTS
The expression levels of human MOF in endometrial carcinoma tissues were significantly higher than that in atypical hyperplasia and normal endometrial tissues. High expression of human MOF was associated with late-stage cancer, lymph node metastasis and short survival time, and it was also an independent prognostic risk factor for endometrial carcinoma. After human MOF knockdown, the proliferation, migration and invasive capacity of Ishikawa cells decreased and cell apoptosis increased. After stimulation with estrogen, the PI3K/Akt and Ras-Raf-MEK-ERK signalling pathways were activated, and the expression of the human MOF protein was increased. human MOF (KAT8) expression showed a positive correlation with ESR1 expression, and KAT8-associated genes were enriched in the cell cycle pathways and splicing pathways.
CONCLUSION
Human MOF was highly expressed in endometrial carcinoma and associated with proliferation. Estrogen/estrogen receptor enhanced human MOF expression; promoted the proliferation, migration and invasion of Ishikawa cells; and inhibited cell apoptosis by activating the PI3K/Akt and Ras-Raf-MEK-ERK signalling pathways.
背景
本研究旨在分析人 MOF 在子宫内膜癌细胞中的表达及其与雌激素和雌激素受体的关系，并探讨雌激素-人 MOF 对子宫内膜癌细胞恶性生物学行为的影响。
方法
采用免疫组织化学法检测不同子宫内膜组织中人 MOF 的表达。通过 Western blot、实时聚合酶链反应、细胞增殖试验和细胞周期分布评估人 MOF、人 MOF 联合雌激素刺激以及雌激素加抗人 MOF 抗体阻断对子宫内膜癌细胞增殖的影响。采用生物信息学方法鉴定人 MOF 和雌激素的相关性及其涉及的途径。
结果
子宫内膜癌组织中人 MOF 的表达水平明显高于非典型增生和正常子宫内膜组织。人 MOF 的高表达与晚期癌症、淋巴结转移和短生存时间相关，是子宫内膜癌的独立预后危险因素。人 MOF 敲低后，Ishikawa 细胞的增殖、迁移和侵袭能力降低，细胞凋亡增加。雌激素刺激后，PI3K/Akt 和 Ras-Raf-MEK-ERK 信号通路被激活，人 MOF 蛋白表达增加。人 MOF（KAT8）表达与人 ESR1 表达呈正相关，KAT8 相关基因富集在细胞周期途径和剪接途径中。
结论
人 MOF 在子宫内膜癌中高表达，并与增殖有关。雌激素/雌激素受体增强人 MOF 的表达；通过激活 PI3K/Akt 和 Ras-Raf-MEK-ERK 信号通路，促进 Ishikawa 细胞的增殖、迁移和侵袭，并抑制细胞凋亡。
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