MicroRNA-driven organ-specific metastasis in triple-negative breast cancer: biogenesis, mechanisms, and therapeutic approaches.

Abstract

MicroRNAs or miRNAs are characterized as non-coding RNAs, and these are the critical regulators of gene expression post-transcription. Emerging evidence highlights their important role in both the progression and repression of cancer. miRNAs, found in both primary tumor cells and circulation, not only regulate primary tumor development but also regulate metastatic progression by affecting the behavior of primary tumor cells and resident cells at distant organs. Metastasis remains a major clinical challenge in cancer treatment, which limits the therapeutic efficacy and reduces patient survival significantly. This challenge is particularly evident in triple-negative breast cancers (TNBC). This malignancy responds poorly to current chemotherapies and lacks reliable biomarkers, thus, it lacks targeted therapy options. Notably, TNBC exhibits a high propensity for metastasis to critical organs such as the brain, bone, liver, and lung. The process of metastasis of TNBC primary tumor remains unclear, which highlights the critical need to uncover its molecular insights and organ-specific biomarkers. As key regulators of metastasis, microRNAs play a vital role in TNBC progression by modulating gene expression in primary tumor cells and functioning as circulating messenger molecules that affect distant metastatic sites. Furthermore, their potential as therapeutic targets are currently being explored in preclinical models, including the development of anti-miRNA oligonucleotides and miRNA mimics. Overall, this review offers an in-depth mechanism of TNBC metastasis and the molecular mechanisms driving the brain, bone, liver, and lung metastasis. The key focus is on understanding the role of miRNAs in directing organ-specific metastasis and evaluating their potential as biomarker for diagnosis and targeted treatment.