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乳脂肪球表皮生长因子8的减少抑制三阴性乳腺癌细胞的活力和迁移。

Reduction in milk fat globule-EGF factor 8 inhibits triple-negative breast cancer cell viability and migration.

作者信息

Yang Yong, Li Jiebao, Song Qi, Zhu Kongjun, Yu Xiaocheng, Tian Ye, Zhang Jiaheng

机构信息

Department of Breast and Thyroid Surgery, Wuhan No. 1 Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.

出版信息

Oncol Lett. 2019 Mar;17(3):3457-3465. doi: 10.3892/ol.2019.9968. Epub 2019 Jan 25.

Abstract

Milk fat globule-EGF factor 8 (MFG-E8) has been demonstrated to be associated with the progression and metastasis of breast cancer, although the underlying mechanisms remain undefined. The aim of the present study was to explore the role of MFG-E8 in human breast cancer and examine the underlying molecular mechanisms. Reverse transcription-quantitative polymerase chain reaction analysis was used to evaluate the expression levels of MFG-E8 in human breast carcinoma cell lines. An MFG-E8 small interfering RNA lentiviral vector was constructed and transfected into MDA-MB-231 cells. The results indicated that the silencing of MFG-E8 significantly inhibited the viability, invasion and migration of breast cancer cells. By using a flow cytometric approach, the knockdown of MFG-E8 was revealed to significantly induce cell cycle arrest at the G2/M phase and cell apoptosis. Furthermore, the downregulation of MFG-E8 induced the activation of apoptosis-associated proteins, and inhibited the expression of matrix metalloproteinase and epithelial-mesenchymal transition-associated proteins. Collectively, the results of the present study emphasize the importance of MFG-E8 deregulation in mammary carcinogenesis and its potential use as a biomarker for the diagnosis of breast carcinomas.

摘要

乳脂肪球表皮生长因子8(MFG-E8)已被证明与乳腺癌的进展和转移有关,但其潜在机制仍不明确。本研究的目的是探讨MFG-E8在人类乳腺癌中的作用,并研究其潜在的分子机制。采用逆转录-定量聚合酶链反应分析评估MFG-E8在人乳腺癌细胞系中的表达水平。构建了MFG-E8小干扰RNA慢病毒载体并转染至MDA-MB-231细胞中。结果表明,MFG-E8的沉默显著抑制了乳腺癌细胞的活力、侵袭和迁移。通过流式细胞术检测发现,MFG-E8的敲低显著诱导细胞周期停滞于G2/M期并诱导细胞凋亡。此外,MFG-E8的下调诱导了凋亡相关蛋白的激活,并抑制了基质金属蛋白酶和上皮-间质转化相关蛋白的表达。总体而言,本研究结果强调了MFG-E8失调在乳腺癌发生中的重要性及其作为乳腺癌诊断生物标志物的潜在用途。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f56e/6396170/7d0e4bcba0b0/ol-17-03-3457-g00.jpg

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