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EGR1 通过诱导 SOX9 表达促进宫颈癌干细胞特性并预测不良预后。

EGR1 promotes stemness and predicts a poor outcome of uterine cervical cancer by inducing SOX9 expression.

机构信息

Department of Gynecology, Affiliated Hospital of Shandong Medical College, Linyi, Shandong, China.

Department of Gynecology, Women and Children's Health Care Hospital of Linyi, Linyi, Shandong, China.

出版信息

Genes Genomics. 2021 May;43(5):459-470. doi: 10.1007/s13258-021-01064-5. Epub 2021 Mar 9.


DOI:10.1007/s13258-021-01064-5
PMID:33687657
Abstract

BACKGROUND: Early growth response-1 (EGR1) is a transcription factor involved in the progression of several cancer types. However, the expression and clinical significance of EGR1 in uterine cervical cancer (CC) have not been elucidated. OBJECTIVE: To investigate the expression, clinical significance and prognostic value of EGR1 in CC. METHODS: The expression of EGR1 was detected in 13 CCs and paired adjacent tissues with qRT-PCR and in 144 CC tissues with immunohistochemistry (IHC). The IHC scores were used to divide the patients into subsets with low and high EGR1 expression. The correlations between the EGR1 expression and clinicopathological factors were analyzed with the chi-square test, and the prognostic significance of EGR1 expression was evaluated with univariate and multivariate analyses. The functions of EGR1 in the proliferation, invasion and stemness of CC cells were investigated, and the molecular mechanism was assessed by in vitro experiments. RESULTS: High expression of EGR1 was significantly associated with low survival rates of CC. EGR1 is an independent prognostic biomarker of CC, and its high expression predicted a poor outcome. EGR1 facilitated stemness and thus promoted proliferation and invasion of CC cells. SOX9 played an essential role in the EGR1-induced progression of CC cells. CONCLUSIONS: EGR1 is an independent prognostic biomarker of CC. High EGR1 expression promoted proliferation, invasion and stemness by increasing SOX9 expression in CC cells. Our results suggested that the EGR1-SOX9 axis may be a potential drug target and that blocking the EGR1-SOX9 axis may be a possible approach to treating CC.

摘要

背景:早期生长反应因子 1(EGR1)是一种参与多种癌症类型进展的转录因子。然而,EGR1 在子宫颈癌(CC)中的表达和临床意义尚未阐明。

目的:研究 EGR1 在 CC 中的表达、临床意义和预后价值。

方法:使用 qRT-PCR 检测 13 例 CC 和配对的相邻组织中的 EGR1 表达,使用免疫组织化学(IHC)检测 144 例 CC 组织中的 EGR1 表达。使用 IHC 评分将患者分为 EGR1 低表达和高表达亚组。使用卡方检验分析 EGR1 表达与临床病理因素的相关性,使用单因素和多因素分析评估 EGR1 表达的预后意义。通过体外实验研究 EGR1 在 CC 细胞增殖、侵袭和干性中的功能,并评估其分子机制。

结果:EGR1 高表达与 CC 患者的低生存率显著相关。EGR1 是 CC 的独立预后生物标志物,其高表达预示着不良预后。EGR1 促进干性,从而促进 CC 细胞的增殖和侵袭。SOX9 在 EGR1 诱导的 CC 细胞进展中起关键作用。

结论:EGR1 是 CC 的独立预后生物标志物。高 EGR1 表达通过增加 CC 细胞中 SOX9 的表达促进增殖、侵袭和干性。我们的结果表明,EGR1-SOX9 轴可能是一个潜在的药物靶点,阻断 EGR1-SOX9 轴可能是治疗 CC 的一种可能方法。

相似文献

[1]
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本文引用的文献

[1]
MAFB Promotes Cancer Stemness and Tumorigenesis in Osteosarcoma through a Sox9-Mediated Positive Feedback Loop.

Cancer Res. 2020-3-31

[2]
SOX9: The master regulator of cell fate in breast cancer.

Biochem Pharmacol. 2020-1-3

[3]
Impaired cardiac performance, protein synthesis, and mitochondrial function in tumor-bearing mice.

PLoS One. 2019-12-18

[4]
Protease Nexin I is a feedback regulator of EGF/PKC/MAPK/EGR1 signaling in breast cancer cells metastasis and stemness.

Cell Death Dis. 2019-9-9

[5]
EGR1 regulates angiogenic and osteoclastogenic factors in prostate cancer and promotes metastasis.

Oncogene. 2019-7-16

[6]
MicroRNA-215-3p suppresses the growth and metastasis of cervical cancer cell via targeting SOX9.

Eur Rev Med Pharmacol Sci. 2019-7

[7]
TBX2 interacts with heterochromatin protein 1 to recruit a novel repression complex to EGR1-targeted promoters to drive the proliferation of breast cancer cells.

Oncogene. 2019-6-28

[8]
Unbalanced YAP-SOX9 circuit drives stemness and malignant progression in esophageal squamous cell carcinoma.

Oncogene. 2018-11-6

[9]
Suppressing serum response factor inhibits invasion in cervical cancer cell lines via regulating Egr‑1 and epithelial-mesenchymal transition.

Int J Mol Med. 2018-10-24

[10]
MicroRNA expression in cervical cancer: Novel diagnostic and prognostic biomarkers.

J Cell Biochem. 2018-8

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