The Role of MicroRNAs in Breast Cancer and the Challenges of Their Clinical Application

Abstract

MicroRNAs (miRNAs) constitute a subclass of non-coding RNAs that exert substantial influence on gene-expression regulation. Their tightly controlled expression plays a pivotal role in various cellular processes, while their dysregulation has been implicated in numerous pathological conditions, including cancer. Among cancers affecting women, breast cancer (BC) is the most prevalent malignant tumor. Extensive investigations have demonstrated distinct expression patterns of miRNAs in normal and malignant breast cells. Consequently, these findings have prompted research efforts towards leveraging miRNAs as diagnostic tools and the development of therapeutic strategies. The aim of this review is to describe the role of miRNAs in BC. We discuss the identification of oncogenic, tumor suppressor and metastatic miRNAs among BC cells, and their impact on tumor progression. We describe the potential of miRNAs as diagnostic and prognostic biomarkers for BC, as well as their role as promising therapeutic targets. Finally, we evaluate the current use of artificial intelligence tools for miRNA analysis and the challenges faced by these new biomedical approaches in its clinical application. The insights presented in this review underscore the promising prospects of utilizing miRNAs as innovative diagnostic, prognostic, and therapeutic tools for the management of BC.

Keywords: MetastamiRs; MicroRNAs; OncomiRs; breast cancer; cancer therapy; diagnosis.

Figure 1

Tumor suppressor miRNAs, oncomiRs, and metastamiRs play critical roles in BC progression. Tumor suppressor miRNAs function to inhibit tumor growth and metastasis by regulating the expression of genes involved in cell cycle control, apoptosis, and DNA repair. Their reduced expression can contribute to uncontrolled cell proliferation, resistance to apoptosis, and increased genomic instability, promoting the development and progression of BC. Conversely, oncomiRs promote oncogenic signaling pathways, cell proliferation, angiogenesis, and invasion. These miRNAs are often overexpressed in BC and target tumor suppressor genes. MetastamiRs contribute to the metastatic cascade. They regulate genes involved in cell adhesion, migration, invasion, and angiogenesis, promoting the dissemination of BC cells to distant sites.

Figure 2

Therapeutic options targeting tumor suppressor miRNAs, oncomiRs, and metastamiRs hold promise for the treatment of BC. Tumor suppressor miRNAs can be therapeutically restored to reestablish their inhibitory functions in BC cells. Various approaches include the use of synthetic miRNA mimics or viral vectors to deliver tumor suppressor miRNAs into cancer cells. By reintroducing these miRNAs, aberrant oncogenic signaling pathways can be suppressed, leading to reduced tumor growth, enhanced apoptosis, and increased sensitivity to chemotherapy. In contrast, therapeutic strategies aiming at oncomiRs involve inhibiting their activity or expression. Thus, by inhibiting oncomiRs, cellular processes promoting tumor growth, invasion, and resistance to treatment can be attenuated. By targeting metastamiRs, it may be possible to impede key steps in the metastatic cascade, such as cell migration, invasion, and angiogenesis.