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MicroRNA-7 suppresses the homing and migration potential of human endothelial cells to highly metastatic human breast cancer cells

Cui, Yuxin, Bradbury, Robyn, Flamini, Valentina ORCID: https://orcid.org/0000-0003-1337-7125, Wu, Bo, Jordan, Nicola and Jiang, Wen Guo ORCID: https://orcid.org/0000-0002-3283-1111 2017. MicroRNA-7 suppresses the homing and migration potential of human endothelial cells to highly metastatic human breast cancer cells. British Journal of Cancer 117 , pp. 89-101. 10.1038/bjc.2017.156

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Abstract

background: MicroRNA-7 (miR-7) has been observed as a potent tumour suppressor in multiple cancer types including breast cancer. The aim of this study was to investigate the response sensitivities of metastatic breast cancer cells to miR-7 and the roles of miR-7 in the interaction of endothelial cells and metastatic cancer cells. methods: Expression profile of miRNAs in a breast cancer specimen cohort and breast cancer cells were determined using real-time quantitative miRNA assays. Effect of the altering expression of miR-7 on migration, invasion, proliferation, interaction and underlying molecular mechanism of breast cancer cells and endothelial cells was investigated after treatment with the synthesised mimic of miR-7. Luciferase activity analysis was performed to validate Wave-3 as a novel target of miR-7. results: miR-7 expression was negatively correlated with the stage, grade and survival of the breast cancer patients. There was also differential expression of miRNAs including miR-7 in the breast cancer cells. The synthesised mimic of miR-7 inhibits the motility and wound healing potential of breast cancer cells. The highly metastatic MDA-MB-231 cells are more sensitive to the miR-7 treatment than the poorly invasive MCF-7 cells. Treatment with miR-7 downregulated the expression of EGFR, IGF1R and Wave3 in MDA-MB-231 cells but not in MCF-7 cells. In addition, we further demonstrated that miR-7 inhibited the proliferation, migration and invasion of endothelial cells. And more importantly, miR-7 suppressed the homing and migration of endothelial cells to more aggressive tumour cell conditions. conclusions: Given the dual inhibitory effect of miR-7 on metastatic breast cancer cells alone and the interaction of endothelial cells with the tumour-conditioned microenvironment, we suggest miR-7 may be a new therapeutic candidate for its capacity not only to prevent breast cancer cell spreading but also to inhibit tumour-associated angiogenesis in the metastatic breast cancer.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Subjects: R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Uncontrolled Keywords: miR-7; breast cancer; endothelial cells; migration; homing; metastasis
Publisher: Nature Publishing Group
ISSN: 0007-0920
Date of First Compliant Deposit: 7 June 2017
Date of Acceptance: 11 May 2017
Last Modified: 02 Nov 2022 11:11
URI: https://orca.cardiff.ac.uk/id/eprint/101123

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