Of these microRNAs, miR-126 restoration reduces overall tumour growth and proliferation, whereas miR-335 inhibits metastatic cell invasion. miR-335 regulates a set of genes whose collective expression in a large cohort of human tumours is associated with risk of distal metastasis. miR-335 suppresses metastasis and migration through targeting of the progenitor cell transcription factor SOX4 and extracellular matrix component tenascin C. Expression of miR-126 and miR-335 is lost in the majority of primary breast tumours from patients who relapse, and the loss of expression of either microRNA is associated with poor distal metastasis-free survival. miR-335 and miR-126 are thus identified as metastasis suppressor microRNAs in human breast cancer.
In addition, miR-126 could target both VEGFA and PIK3R2, and its expression was decreased in human breast cancer, implying that miR-126 may play a role in tumor genesis and growth by regulating the VEGF/PI3K/AKT signaling pathway.
Co-injection of endothelial cells with breast cancer cells non-cell-autonomously rescues their miR-126-induced metastatic defect, revealing a novel and important role for endothelial interactions in metastatic initiation.
Specific miRNAs (mir-10, mir-21, mir-155, mir-373, mir-30b, mir-126, mir-17p, mir-335) are associated with tumor metastasis and other clinical characteristics for BC, facilitating identification of individuals who are at risk.
Finally, we further revealed that miR-126 silencing could impair the suppressive function of Tregs in vivo and endow effectively antitumour effect of CD8(+) T cells in adoptive cell transfer assay using a murine breast cancer model.
These findings determine how this microRNA pair alters the composition of the primary tumour microenvironment to favour breast cancer metastasis, and demonstrate a correlation between miR-126/126(*) downregulation and poor metastasis-free survival of breast cancer patients.
In summary, mango polyphenolics have a chemotherapeutic potential against breast cancer that at least in part is mediated through the PI3K/AKT pathway and miR-126.
Thus, our study revealed that miR-126 may act as a tumor suppressor via inhibition of cell invasion by downregulating ADAM9 in breast cancer development.
We propose that miR-126 and miR-218 have a protective role in DCIS and represent novel biomarkers for the risk assessment in women with early detection of breast cancer.
Patients with breast cancer with increased miRNA-21 and miRNA-155 and decreased miRNA-126 expressions had significantly worse disease-free survival, while only miRNA-21 and miRNA-126 showed poor OS (P< 0.005).
Thus, miR-124 and miR-126 may be involved in the occurrence, development, invasion and metastasis of BC, and both can be used as targeted biological indexes for treatment of BC.
Analysis of our BrCa signature revealed that several miRNA duplexes (guide strand/passenger strand) derived from pre-miRNAs were downregulated in BrCa tissues (e.g., miR-99a-5p/-3p, miR-101-5p/-3p, miR-126-5p/-3p, miR-143-5p/-3p, and miR-144-5p/-3p).