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锌指蛋白652高表达促进乳腺癌的发生发展

[High expression of ZNF652 promotes carcinogenesis and progression of breast cancer].

作者信息

Lei Ting, Xiao Bin, He Yongyin, Sun Zhaohui, Li Linhai

机构信息

Guangzhou University of Chinese Medicine, Guangzhou 510405, China.

Department of Laboratory Medicine, General Hospital of Southern Theatre Command of PLA, Guangzhou 510010, China.

出版信息

Nan Fang Yi Ke Da Xue Xue Bao. 2020 Dec 30;40(12):1732-1739. doi: 10.12122/j.issn.1673-4254.2020.12.06.

Abstract

OBJECTIVE

To investigate the expression of ZNF652 in breast cancer tissues and cells and explore its role in breast cancer cell proliferation, invasion and migration.

METHODS

We exploited the data from the TCGA database to analyze the differential expression of ZNF652 in breast cancer tissues and adjacent tissues and the correlations of ZNF652 expression with the clinicopathological characteristics of breast cancer patients including molecular subtypes, pathological types, TNM stages and clinical stages. RT-qPCR and Western blotting were used to detect the expression of ZNF652 in 5 breast cancer cell lines including MCF-7, MDA-MB-231, SK-BR-3, UACC-812 and BT-474. Using a lentivirus system and siRNA technique, we assessed the effects of ZNF652 over-expression and knockdown on proliferation, colony forming ability, migration and invasion of breast cancer cells with CCK-8 assay, clonogenic assay, Transwell assay and wound healing assay. The subcellular localization of ZNF652 in 293T cells was determined using immunofluorescence assay.

RESULTS

ZNF652 was significantly up-regulated in breast cancer tissues ( < 0.001). In breast cancer tissues of different molecular types, ZNF652 was down-regulated in TNBC breast cancer tissues but increased in HER2+, Luminal A and Luminal B breast cancer tissues ( < 0.01 or 0.001). The expression of ZNF652 was significantly higher in breast cancer tissues of all pathological types except for mucinous carcinoma than in the adjacent tissues ( < 0.05). The high expression of ZNF652 was closely related to distant metastasis and malignancy of breast cancer ( < 0.01 or 0.001). The mRNA and protein expression levels of ZNF652 was significantly higher in the 5 breast cancer cell lines than in normal breast cells ( < 0.05 or 0.001). Overexpression of ZNF652 promoted the proliferation, invasion and migration of breast cancer cells, while ZNF652 knockdown produced the opposite effects ( < 0.05). Immunofluorescence assay identified subcellular localization of ZNF652 in the nuclei of 293T cells.

CONCLUSIONS

ZNF652 is highly expressed in breast cancer tissues and cells to promote the development and progression of breast cancer and may serve as a potential molecular target for diagnosis and treatment of the malignancy.

摘要

目的

研究ZNF652在乳腺癌组织和细胞中的表达情况,并探讨其在乳腺癌细胞增殖、侵袭和迁移中的作用。

方法

利用TCGA数据库的数据,分析ZNF652在乳腺癌组织和癌旁组织中的差异表达,以及ZNF652表达与乳腺癌患者临床病理特征(包括分子亚型、病理类型、TNM分期和临床分期)的相关性。采用RT-qPCR和蛋白质免疫印迹法检测ZNF652在5种乳腺癌细胞系(MCF-7、MDA-MB-231、SK-BR-3、UACC-812和BT-474)中的表达。利用慢病毒系统和小干扰RNA技术,通过CCK-8检测法、克隆形成试验、Transwell试验和伤口愈合试验,评估ZNF652过表达和敲低对乳腺癌细胞增殖、集落形成能力、迁移和侵袭的影响。采用免疫荧光试验确定ZNF652在293T细胞中的亚细胞定位。

结果

ZNF652在乳腺癌组织中显著上调(<0.001)。在不同分子类型的乳腺癌组织中,ZNF652在三阴乳腺癌组织中下调,但在HER2+、Luminal A和Luminal B乳腺癌组织中上调(<0.01或<0.001)。除黏液癌外,ZNF652在所有病理类型的乳腺癌组织中的表达均显著高于癌旁组织(<0.05)。ZNF652的高表达与乳腺癌的远处转移和恶性程度密切相关(<0.01或<0.001)。ZNF652在5种乳腺癌细胞系中的mRNA和蛋白质表达水平均显著高于正常乳腺细胞(<0.05或<0.001)。ZNF652过表达促进乳腺癌细胞的增殖、侵袭和迁移,而ZNF652敲低则产生相反的效果(<0.05)。免疫荧光试验确定ZNF652在293T细胞核中的亚细胞定位。

结论

ZNF652在乳腺癌组织和细胞中高表达,促进乳腺癌的发生和发展,可能成为恶性肿瘤诊断和治疗的潜在分子靶点。

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