Lema Noubani

Introduction. Breast cancer is the world’s leading cause in cancer-related death in women¹. About 1 in 10 women will get breast cancer in their lifetime¹. Early breast cancer detection is potentially curable, so looking for ways to detect it early leads to a better prognosis. Poor prognosis is correlated with increased angiogenesis, which is the formation of new blood vessels. This process aids in the growth and metastasis of breast cancer and is mediated by vascular endothelial growth factor (VEGF)². Vascular endothelial growth factor plays an important role in the progression of breast cancer through its effects on neovascularization². It is a part of a subfamily of the platelet derived growth factor family that promotes the division of endothelial cells and the fusion of blood vessels to meet the increasing metabolic demands of growing tissue². The upregulation of this system in breast cancer leads to increased tumor growth and metastasis ultimately resulting in a poor prognosis. In normal tissue, VEGF expression is regulated by microRNAs (miRNA)³. In this study, two microRNAs’ effects on the expression of VEGF were evaluated in breast cancer cells in hopes of their use as a biomarker or as potential therapy. Methods. Breast cancer derived cells, MDA-MB-231 & MCF-7, that show high expression of VEGF were isolated from breast cancer patients^4,5. MiR-140-5p and miR-100 were transfected into both cell types and the expression of VEGF was measured. Human umbilical vein endothelial cells (HUVECs) were also added to miRNA conditioned media, and the level of capillary-like vessel formation was recorded^4,5. Mice tumors were also injected with the miRNAs, and the tumor volume was measured. Results. The levels of miRNA were shown to be downregulated, as the breast cancer stages progress⁵. This is correlated with the increased levels of VEGF associated with the progression. When the breast cancer-derived cells were injected with the miRNAs, there was a significant downregulation in the levels of VEGF mRNA expression, protein secretion, and VEGF receptor expression^4,5. The HUVEC assays showed a decrease in micro-vessel formation through decreased tubing and branching in miRNA conditioned media^4,5. The mice tumor volume significantly decreased under the miRNA injection, as well⁵. Conclusion. miR-100 acts on the mTOR/HIF-1α signaling pathway and miR-140-5p directly binds the 3’UTR of the VEGF gene, but both downregulate the production of VEGF, and ultimately slow the progression of breast cancer^4,5. These miRNAs act as promising biomarkers and/or therapy for breast cancer.

1. Harbeck N, Gnant M. Breast cancer. Lancet. 2017;389(10074):1134–1150. doi:10.1016/S0140-6736(16)31891-8
2. Shibuya, M. (2011). Vascular endothelial growth factor (VEGF) and its receptor (VEGFR) signaling in angiogenesis: a crucial target for anti-and pro-angiogenic therapies. Genes & cancer, 2(12), 1097-1105.
3. Syed, S. N., & Brüne, B. (2020). MicroRNAs as Emerging Regulators of Signaling in the Tumor Microenvironment. Cancers, 12(4), 911.
4. Pakravan, K., Babashah, S., Sadeghizadeh, M., Mowla, S. J., Mossahebi-Mohammadi, M., Ataei, F., … & Javan, M. (2017). MicroRNA-100 shuttled by mesenchymal stem cell-derived exosomes suppresses in vitro angiogenesis through modulating the mTOR/HIF-1α/VEGF signaling axis in breast cancer cells. Cellular oncology, 40(5), 457-470.
5. Lu, Y., Qin, T., Li, J., Wang, L., Zhang, Q., Jiang, Z., & Mao, J. (2017). MicroRNA-140-5p inhibits invasion and angiogenesis through targeting VEGF-A in breast cancer. Cancer gene therapy, 24(9), 386-392.