miRNAs in Health and Disease: A Focus on the Breast Cancer Metastatic Cascade towards the Brain

Abstract

MicroRNAs (miRNAs) are small non-coding RNAs that mainly act by binding to target genes to regulate their expression. Due to the multitude of genes regulated by miRNAs they have been subject of extensive research in the past few years. This state-of-the-art review summarizes the current knowledge about miRNAs and illustrates their role as powerful regulators of physiological processes. Moreover, it highlights their aberrant expression in disease, including specific cancer types and the differential hosting-metastases preferences that influence several steps of tumorigenesis. Considering the incidence of breast cancer and that the metastatic disease is presently the major cause of death in women, emphasis is put in the role of miRNAs in breast cancer and in the regulation of the different steps of the metastatic cascade. Furthermore, we depict their involvement in the cascade of events underlying breast cancer brain metastasis formation and development. Collectively, this review shall contribute to a better understanding of the uniqueness of the biologic roles of miRNAs in these processes, to the awareness of miRNAs as new and reliable biomarkers and/or of therapeutic targets, which can change the landscape of a poor prognosis and low survival rates condition of advanced breast cancer patients.

MicroRNAs and Extracellular Vesicles as Distinctive Biomarkers of Precocious and Advanced Stages of Breast Cancer Brain Metastases Development

“…Extracellular vesicles (EVs) and/or small, non-coding regulatory micro RNAs (miRNAs or miR) found in the circulation encompass new candidate disease biomarkers worth exploring. In fact, both can be detected in body fluids, holding a role as potential tumor markers and prognostic factors, and providing a powerful minimally-invasive approach for tumor progression assessment [ 6 , 7 , 8 ].…”

“…Besides EVs, miRNAs have arisen as powerful and specific biomarkers for different types of cancer and metastasis, having unique expression profiles, depending not only on the type of cancer but also on the disease stage [ 8 , 25 , 26 ]. miRNAs are short noncoding RNAs of approximately 18–22 nucleotides that play a significant role in the regulation of multiple genes, modulating a plethora of cellular processes, including cell survival, apoptosis, carcinogenesis, and metastasis [ 27 ].…”

“…miRNAs are short noncoding RNAs of approximately 18–22 nucleotides that play a significant role in the regulation of multiple genes, modulating a plethora of cellular processes, including cell survival, apoptosis, carcinogenesis, and metastasis [ 27 ]. Therefore, dysregulation of miRNAs has a prominent role in cancer, and specific ones can be either upregulated or downregulated in different types of the disease, possibly functioning as oncogenes or as tumor suppressors [ 8 , 28 ]. Circulating miRNAs can be of special interest, due to their stability and easy quantification in biological fluids, allowing their usage in liquid biopsies for diagnosis and prognosis of oncological diseases [ 6 , 29 ].…”

Hsa-mir-548 family expression in human reproductive tissues

“…The seed sequences of miRNAs, the 2-7 nucleotides positioned in the 5′ region, play an important role in the precise targeting of mRNA [2,3], while other regions in the miRNA sequence complement the target's specificity [4]. Overall, miRNAs play wellestablished roles in gene expression regulation in normal and pathological conditions [5]. Moreover, different tissues demonstrate variable miRNA expression patterns that determine tissue characteristics, differentiation, and functions [6].…”

Cerebral Metastasis of Common Cancers

“…While this effect was found in estrogen receptor-negative breast cancers, no such mechanism seems to be prominent in lung cancer. The expression of sets of microRNAs are operative in the metastatic cascade to the brain as well [ 16 ] and micro-environmental factors and interactions between the residential and metastatic cells are topics of current research [ 17 , 18 ]. Part of the molecular mechanisms underlying the passage of tumor cells through the BBB implicate motility of the tumor cells [ 19 ].…”