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ZBTB7A 通过 NF-κB 诱导的上皮-间充质转化促进人乳腺癌细胞的迁移、侵袭和转移,在体内外。

ZBTB7A promotes migration, invasion and metastasis of human breast cancer cells through NF-κB-induced epithelial-mesenchymal transition in vitro and in vivo.

机构信息

Department of Breast Surgery, Guangxi Medical University Cancer Hospital, 71 Hedi Road, Qingxiu District, Nanning 530021, Guangxi Province, China.

出版信息

J Biochem. 2019 Dec 1;166(6):485-493. doi: 10.1093/jb/mvz062.

Abstract

It has been generally confirmed that zinc finger and BTB domain containing 7A (ZBTB7A) plays an important role in the occurrence and progression of malignant tumours, but the promotion or inhibition effect is related to tumour type. The mechanism between ZBTB7A and breast cancer is not well understood, so further research is needed. In this study, we first investigated the expression of ZBTB7A in tissue samples of clinical breast cancer patients, MDA-MB-231, MCF-7 and MCF-10A cells. Second, we overexpressed the ZBTB7A in MCF-7 cells and silenced the ZBTB7A in MDA-MB-231 cells using lentivirus transfection technology, respectively, and verified the effect of ZBTB7A on migration and invasion of breast cancer cell lines through in vitro cell function experiments, such as wound-healing assay, migration and invasion assay, quantitative real time reverse transcriptase (qRT-PCR) and western blot. Then, the correlation between the above influences, epithelial-mesenchymal transition (EMT) and NF-κB was analysed. Finally, in vivo tumour transplantation model in nude mice was established to verified the effect of ZBTB7A on metastasis of breast cancer MDA-MB-231 cells. In conclusion, ZBTB7A is highly expressed in cancer tissue, breast cancer cell line MDA-MB-231 and MCF-7. Meanwhile, the high expression of ZBTB7A may promote cell migration, invasion and tumour metastasis, which may be related to EMT events by regulating NF-κB.

摘要

已普遍证实锌指和 BTB 结构域包含蛋白 7A(ZBTB7A)在恶性肿瘤的发生和进展中发挥重要作用,但促进或抑制作用与肿瘤类型有关。ZBTB7A 与乳腺癌之间的机制尚不清楚,因此需要进一步研究。在这项研究中,我们首先研究了 ZBTB7A 在临床乳腺癌患者组织样本、MDA-MB-231、MCF-7 和 MCF-10A 细胞中的表达。其次,我们使用慢病毒转染技术分别在 MCF-7 细胞中转染过表达 ZBTB7A,在 MDA-MB-231 细胞中沉默 ZBTB7A,并通过体外细胞功能实验(如划痕愈合实验、迁移和侵袭实验、定量实时逆转录聚合酶链反应(qRT-PCR)和 Western blot)验证 ZBTB7A 对乳腺癌细胞系迁移和侵袭的影响。然后,分析了上述影响、上皮-间充质转化(EMT)和 NF-κB 之间的相关性。最后,建立了裸鼠体内肿瘤移植模型,以验证 ZBTB7A 对乳腺癌 MDA-MB-231 细胞转移的影响。总之,ZBTB7A 在癌组织、乳腺癌细胞系 MDA-MB-231 和 MCF-7 中高表达。同时,ZBTB7A 的高表达可能通过调节 NF-κB 促进细胞迁移、侵袭和肿瘤转移,这可能与 EMT 事件有关。

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