Angioregulatory microRNAs in breast cancer: Molecular mechanistic basis and implications for therapeutic strategies

[Display omitted] •Cancer-associated angiogenesis is a fundamental process in tumor growth and metastasis.•Angioregulatory miRNA–target gene interaction is not only involved in sprouting vessels of breast tumors but also, trans-differentiation of breast cancer cells to endothelial cells in a process termed vasculogenic mimicry.•Successful targeting of tumor angiogenesis is still a missing link in the treatment of Breast cancer (BC) due to the low effectiveness of anti-angiogenic therapies in this cancer.•Response to anti-angiogenic therapeutics are controlled by a miRNAs, so the identification of interaction networks of miRNAs–targets can be applicable in determining anti-angiogeneic therapy and new biomarkers in BC.•Angioregulatory miRNAs in breast cancer cells and their microenvironment have therapeutic potential in cancer treatment. Cancer-associated angiogenesis is a fundamental process in tumor growth and metastasis. A variety of signaling regulators and pathways contribute to establish neovascularization, among them as small endogenous non-coding RNAs, microRNAs (miRNAs) play prominent dual regulatory function in breast cancer (BC) angiogenesis. This review aims at describing the current state-of-the-art in BC angiogenesis-mediated by angioregulatory miRNAs, and an overview of miRNAs dysregulation association with the anti-angiogenic response in addition to potential clinical application of miRNAs-based therapeutics. Angioregulatory miRNA–target gene interaction is not only involved in sprouting vessels of breast tumors but also, trans-differentiation of BC cells to endothelial cells (ECs) in a process termed vasculogenic mimicry. Using canonical and non-canonical angiogenesis pathways, the tumor cell employs the oncogenic characteristics such as miRNAs dysregulation to increase survival, proliferation, oxygen and nutrient supply, and treatment resistance. Angioregulatory miRNAs in BC cells and their microenvironment have therapeutic potential in cancer treatment. Although, miRNAs dysregulation can serve as tumor biomarker nevertheless, due to the association of miRNAs dysregulation with anti-angiogenic resistant phenotype, clinical benefits of anti-angiogenic therapy might be challenging in BC. Hence, unveiling the molecular mechanism underlying angioregulatory miRNAs sparked a booming interest in finding new treatment strategies such as miRNA-based therapies in BC.