Abstract
Simple SummaryMicroRNAs (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.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.
Highlights
Breast cancer is the most commonly diagnosed cancer in women worldwide [1].Increased awareness, improved screening methods, and novel treatment strategies have had a significant impact on disease management, and survival rates for patients with primary breast cancer are above 90% [2]
Once disseminated breast cancer cells proliferate in bone, the tumor–bone cell interactions result in accelerated osteoclast-mediated bone resorption, a key characteristic of the disease
Breast cancer cells expressing miR-124 had significantly lower messenger RNA (mRNA) and protein levels of IL-11 when compared to control [46]. This observation, in addition to complementary in vitro and in vivo studies using IL11 neutralizing antibodies and recombinant human IL-11, demonstrated that miR-124 induced downregulation of IL-11 is partially responsible for reduced breast cancer bone metastasis [46]
Summary
Breast cancer is the most commonly diagnosed cancer in women worldwide [1]. Increased awareness, improved screening methods, and novel treatment strategies have had a significant impact on disease management, and survival rates for patients with primary breast cancer are above 90% [2]. Patients suffering from breast cancer bone metastasis are confronted with a tremendous reduction in quality of life, predominantly due to the accelerated cancer-induced bone loss. They often suffer from skeletal-related events (SREs) such as bone pain, spinal cord compression, fractures, and increased morbidity [5]. Significant progress has been made in identifying and characterizing the cellular and molecular composition of the bone metastasis niche [14,15,16,17,18], which includes the HSC, endosteal (osteoblasts, osteoclasts, fibroblasts), and vascular (endothelial cells) niches [14,16]. The precise location of these niches remains to be defined; the extent to which these niches overlap and/or interact remains challenging to elaborate
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