MicroRNAs: Emerging Regulators of Metastatic Bone Disease in Breast Cancer

SIMPLE SUMMARY: MicroRNAs (miRNAs) are short RNA molecules that can interfere with messenger RNA and thus influence protein translation. In recent years, it has been revealed that miRNAs are also involved in carcinogenesis. However, the effect of each miRNA can differ significantly, and they may exhibit pro-tumorigenic or anti-tumorigenic properties. Breast cancer is one of the most common cancer entity in women and distant metastases are frequently observed in the skeleton. The progression of breast cancer bone metastasis largely depends on the interaction of tumor cells and cells of the bone microenvironment. In this review, we summarize the current findings related to miRNAs in metastatic bone disease with a focus on breast cancer. This review emphasizes the impact of miRNAs on both cancer cells and key cells of the bone microenvironment. Additionally, we discuss the potential use of miRNAs as a therapeutic target and elaborate advantages and hurdles of miRNA treatment. ABSTRACT: Bone metastasis is a frequent complication in patients with advanced breast cancer. Once in the bone, cancer cells disrupt the tightly regulated cellular balance within the bone microenvironment, leading to excessive bone destruction and further tumor growth. Physiological and pathological interactions in the bone marrow are mediated by cell–cell contacts and secreted molecules that include soluble proteins as well as RNA molecules. MicroRNAs (miRNAs) are short non-coding RNAs that post-transcriptionally interfere with their target messenger RNA (mRNA) and subsequently reduce protein abundance. Since their discovery, miRNAs have been identified as critical regulators of physiological and pathological processes, including breast cancer and associated metastatic bone disease. Depending on their targets, miRNAs can exhibit pro-tumorigenic or anti-tumorigenic functions and serve as diagnostic and prognostic biomarkers. These properties have encouraged pre-clinical and clinical development programs to investigate miRNAs as biomarkers and therapeutic targets in various diseases, including metastatic cancers. In this review, we discuss the role of miRNAs in metastatic bone disease with a focus on breast cancer and the bone microenvironment and elaborate on their potential use for diagnostic and therapeutic purposes in metastatic bone disease and beyond.