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

Abstract

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.

The Cell-Free Expression of MiR200 Family Members Correlates with Estrogen Sensitivity in Human Epithelial Ovarian Cells

“…Our results suggest that cell-free miR200b and miR200c might be possible players of this process in ovarian cancer due to their supposed delivery to neighboring cells. It is interesting to mention that these miRNAs were able to affect the phenotype of several cell types in previous studies that favored tumor growth as well as cancer immune escape [ 67 , 68 , 69 , 70 ]. It is important to note that the presence of cell lysis or apoptosis was ruled out during the tested conditions, which suggests the active secretion of these miRNAs to the extracellular environment, a process which was also suggested by others [ 71 ].…”

miRNAs in the Regulation of Cancer Immune Response: Effect of miRNAs on Cancer Immunotherapy

“…We have also discussed the way that miRNA modulates immunogenic cells in the microenvironment of tumours. Therefore, miRNA emerges as a potential future therapeutic tool against cancer treatment [ 187 ]. Currently, two broad categories of microRNA, i.e., miRNA mimics and miRNA inhibitory therapy, are being explored to determine their role as an immunotherapeutic agent in managing and treating cancer.…”

Bone, a Secondary Growth Site of Breast and Prostate Carcinomas: Role of Osteocytes

“…Cancer cells with malignant potential develop various strategies to reach secondary growth sites: they escape immunosurveillance [ 5 , 6 ], degrade the basement membrane and the extra cellular matrix (ECM), invade the surrounding microenvironment (local invasion), and enter the bloodstream and/or the lymphatic system, ultimately reaching sites where they will give rise to metastatic growth [ 3 , 7 , 8 ]. Bone metastasis differs in aspect depending on the interactions between the cancer cells and the complex tissue microenvironment.…”