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

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.

microRNA Regulation in Estrogen Receptor-Positive Breast Cancer and Endocrine Therapy

“…miR-7 expression is elevated in ER + breast cancer cell lines and is associated with tumor aggressiveness, as indicated by the positive correlation between miR-7 expression and increased tumor size, grade, and metastasis in ER + breast cancer patients [ 8 , 50 , 51 ]. In contrast, miR-7 expression is inversely correlated with the invasiveness of breast cancer cell lines in vitro [ 52 ]. Moreover, miR-7 is reported to influence the G2/M cell cycle checkpoint and DNA repair via inhibition of key regulators, such as WEE1 , GADD45A , TP53 , and ATM [ 50 ], which contributes to the reduced proliferative phenotype observed breast cancer cells overexpressing miR-7 [ 53 ].…”

hsa_circRNA_0006528 as a competing endogenous RNA promotes human breast cancer progression by sponging miR‐7‐5p and activating the MAPK/ERK signaling pathway

“…miR‐7‐5p was downregulated and functions as a potent tumor suppressor in multiple cancer types, including breast cancer . In prior research, miR‐7 expression was negatively correlated with stage, grade and survival for breast cancer patients, and overexpression of miR‐7 inhibited the proliferation, invasion, and migration of breast cancer cells …”

MicroRNA‐93 targets WASF3 and functions as a metastasis suppressor in breast cancer

“…WASF3 downregulates miR‐200 family miRNAs, suppressors of EMT, during tumor progression, 11‐13 suggesting that WASF3 and miR‐200 play a key role in controlling the invasion‐metastasis cascade of cancer cells. WASF3 is one of the targets of miRNAs, such as miR‐7 and miR‐217, that inhibit the motility and/or metastatic potential of cancer cells 14,15 …”