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CDC20通过稳定NLRP3的表达促进食管癌细胞增殖的研究
CDC20 facilitates the proliferation of esophageal carcinoma cell by stabilizing NLRP3 expression
- 中国癌症杂志 2024年34卷第5期 页码：473-484
- 作者机构：
1. 新乡医学院健康中原研究院，新乡市分子癌学重点实验室，河南 新乡 453003
2. 新乡医学院第三附属医院消化内科，河南 新乡 453003
3. 复旦大学附属肿瘤医院肿瘤研究所，复旦大学上海医学院肿瘤学系，上海 200032
4. 新乡医学院基础医学院，河南 新乡 453003
5. 新乡医学院第一附属医院消化内科，河南 新乡 453003
- 作者简介：
[ "关瑞瑞（ORCID: 0009-0000-0235-0723），硕士。" ]
周祥（ORCID: 0000-0002-1172-7948），博士，研究员。
韩涛（ORCID: 0000-0002-5943-8520），博士，教授；
- 基金信息：国家自然科学基金(81972330)
DOI：10.19401/j.cnki.1007-3639.2024.05.004
中图分类号： R735.1收稿：2023-12-27，
修回：2024-03-06，
纸质出版：2024-05-30
- 稿件说明：
移动端阅览
关瑞瑞, 郝茜, 张雅琦, 等. CDC20通过稳定NLRP3的表达促进食管癌细胞增殖的研究[J]. 中国癌症杂志, 2024,34(5):473-484.
Ruirui GUAN, Qian HAO, Yaqi ZHANG, et al. CDC20 facilitates the proliferation of esophageal carcinoma cell by stabilizing NLRP3 expression[J]. China Oncology, 2024, 34(5): 473-484.
关瑞瑞, 郝茜, 张雅琦, 等. CDC20通过稳定NLRP3的表达促进食管癌细胞增殖的研究[J]. 中国癌症杂志, 2024,34(5):473-484. DOI： 10.19401/j.cnki.1007-3639.2024.05.004.
Ruirui GUAN, Qian HAO, Yaqi ZHANG, et al. CDC20 facilitates the proliferation of esophageal carcinoma cell by stabilizing NLRP3 expression[J]. China Oncology, 2024, 34(5): 473-484. DOI： 10.19401/j.cnki.1007-3639.2024.05.004.
摘要
背景与目的：
食管癌（esophageal carcinoma，ESCA）是死亡率较高的恶性肿瘤之一，其发生、发展的机制不明。
CDC
20被认为具有癌基因功能，其表达失调与肿瘤的发生、发展密切相关。CDC20在多种肿瘤中表达升高，敲低CDC20能够抑制肿瘤细胞增殖。NLRP3是炎症小体的主要成分之一，炎症小体失调与肿瘤的发生、发展也密切相关。本研究旨在探究CDC20是否通过NLRP3促进ESCA细胞增殖，同时分析其调控机制。
方法：
通过癌症基因组图谱（The Cancer Genome Atlas，TCGA）数据库和GTEx公共数据库分析ESCA患者中
CDC
20和
NLRP
3基因的表达水平。收集新乡医学院第一附属医院收治的80例ESCA患者的临床病理学资料和组织，通过免疫组织化学染色检测NLRP3在ESCA患者中的蛋白表达水平。本研究通过新乡医学院第一附属医院伦理委员会的审批（编号：EC-021-137）。通过短发夹RNA（short hairpin RNA，shRNA）技术检测敲低
CDC
20和
NLRP
3基因后对食管鳞状细胞癌细胞系EC9706和KYSE150增殖能力的影响。通过免疫共沉淀（Co-immunoprecipitation，Co-IP）、蛋白酶体抑制剂和泛素化实验检测CDC20是否与NLRP3相互作用，以及阐明CDC20是否通过泛素化途径调控NLRP3表达。
结果：
TCGA数据库分析结果显示，ESCA组织中CDC20和NLRP3 mRNA表达水平明显高于癌旁组织。免疫组织化学结果也进一步显示，与癌旁组织相比，CDC20、NLRP3在ESCA组织中蛋白表达水平升高。敲低
CDC
20和
NLRP
3基因可抑制ESCA细胞增殖。Co-IP、蛋白酶体抑制剂和泛素化实验证实CDC20通过NLRP3的LRR区与NLRP3相互作用，且CDC20通过促进NLRP3泛素化稳定其表达。
结论：
CDC20和NLRP3在ESCA癌组织中表达上调，且CDC20通过泛素化NLRP3稳定其表达，从而促进ESCA细胞增殖，提示CDC20和NLRP3可能是ESCA潜在的诊断靶向标志物。
Abstract
Background and purpose:
Esophageal carcinoma (ESCA) is one of the malignant tumors with high mortality rate
and the underlying mechanism of its development is largely unknown.
CDC
20 plays an important role in tumorigenesis
and its dysregulated expression is closely related to tumor occurrence and development. The expression of CDC20 is increased in a variety of tumors
and knocking down
CDC
20 can inhibit tumor cell proliferation. NLRP3 is the main component of the inflammasome
and inflammasome is also closely related to tumor occurrence and development. Here
our study aimed to investigate whether CDC20 promotes the proliferation of ESCA cells through NLRP3 and its regulatory mechanism
.
Methods:
The expression levels of
CDC
20 and
NLRP
3 genes in ESCA patients were analyzed using The Cancer Genome Atlas (TCGA) detabase and GTEx public database. We collected clinical and pathological data and tissues from 80 ESCA patients at the First Affiliated Hospital of Xinxiang Medical College
and detected the protein expression of NLRP3 in ESCA patients through immunohistochemistry staining. This study was approved by the Ethics Committee of the First Affiliated Hospital of Xinxiang Medical College (Number: EC-021-137). We studied the effects of knocking down
CDC
20 and
NLRP
3 gene on the proliferation ability of esophageal squamous cell carcinoma cells EC9706 and KYSE150 using short hairpin RNA (shRNA) technology. Co-immunoprecipitation (Co-IP)
proteasome inhibitors and ubiquitination experiments were used to detect whether CDC20 interacts with NLRP3
and to elucidate whether CDC20 regulates NLRP3 expression through the ubiquitination pathway. This study was approved by the Ethics Committee of the First Affiliated Hospital of Xinxiang Medical College (Number: EC-021-137).
Results:
The TCGA database analysis showed that the expression levels of CDC20 and NLRP3 mRNA were significantly higher in the cancer tissues of ESCA patients than in the adjacent tissues. The immunohistochemistry results further showed that compared with adjacent tissues
the protein expression levels of CDC20 and NLRP3 were increased in ESCA tissues. Knocking down
CDC
20 and
NLRP
3 genes inhibited the proliferation of ESCA cells. Co-IP
proteasome inhibitors and ubiquitination experiments confirmed that CDC20 interacted with NLRP3 through its leucine-rich repeat (LRR)
and CDC20 stabilized its expression by promoting NLRP3 ubiquitination.
Conclusion:
CDC20 and NLRP3 are upregulated in ESCA tissues
and CDC20 stabilizes their expression through ubiquitination of NLRP3
promoting ESCA cell proliferatio
n. This suggests that CDC20 and NLRP3 may be potential diagnostic targets for ESCA.
关键词
Keywords
references
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