microRNAs in the Antitumor Immune Response and in Bone Metastasis of Breast Cancer: From Biological Mechanisms to Therapeutics.

Breast cancer is the most common type of cancer in women, and the occurrence of metastasis drastically worsens the prognosis and reduces overall survival. Understanding the biological mechanisms that regulate the transformation of malignant cells, the consequent metastatic transformation, and the immune surveillance in the tumor progression would contribute to the development of more effective and targeted treatments. In this context, microRNAs (miRNAs) have proven to be key regulators of the tumor-immune cells crosstalk for the hijack of the immunosurveillance to promote tumor cells immune escape and cancer progression, as well as modulators of the metastasis formation process, ranging from the preparation of the metastatic site to the transformation into the migrating phenotype of tumor cells. In particular, their deregulated expression has been linked to the aberrant expression of oncogenes and tumor suppressor genes to promote tumorigenesis. This review aims at summarizing the role and functions of miRNAs involved in antitumor immune response and in the metastasis formation process in breast cancer. Additionally, miRNAs are promising targets for gene therapy as their modulation has the potential to support or inhibit specific mechanisms to negatively affect tumorigenesis. With this perspective, the most recent strategies developed for miRNA-based therapeutics are illustrated.