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.
Highlights
Metastatic cancer is a main cause of death, and early diagnosis of the primary tumor, as well as the constant monitoring of disease progression and the patient’s response to therapies and surgery, are essential to efficiently manage subjects with cancer
The increasing knowledge of the biological mechanisms underlying the transformation and consequent metastatic transition has brought the discovery of new therapeutic targets and the development of more and more effective treatments that act on metastasis and/or on the primary tumor in order to limit the risk of metastasis
Compared to ER− breast tumors, ER+ breast tumors are positively correlated to the presence of clusters of innate immune cells that favor a good prognosis: natural killer (NK) cells have antitumor activity in ER+ breast cancers, their numbers decrease in advanced tumor stages [24,25,26]
Summary
Metastatic cancer is a main cause of death, and early diagnosis of the primary tumor, as well as the constant monitoring of disease progression and the patient’s response to therapies and surgery, are essential to efficiently manage subjects with cancer. Circulating miRNAs are promising markers for cancer diagnosis, prognosis, monitoring the treatment response, and as powerful tools for personalized approaches [3] Since their biological relevance and the more and more deepened knowledge about the biological mechanisms associated with their expression in both physiological and pathological conditions, novel therapeutic approaches targeting or inducing miRNAs are, currently, under study. The aim of this narrative review is to summarize the most recent findings relative to the miRNA-dependent regulation of immunosurveillance and immune-escaping of metastasizing breast cancer with a specific focus on bone metastasis. Information about miRNAs can be found in databases such as miRBase (www.mirbase.org) [19] and MirGeneDB (http://mirgenedb.org) [20], which are continuously updated to an impressively growing number of discoveries around miRNAs
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