The role of MiRNA-mediated tumor microenvironment in bone metastasis from a multi-omics perspective: cross-cancer mechanisms and clinical translation.

Bone metastasis is a highly prevalent complication in patients with advanced prostate, breast, and lung cancers, which significantly affects the patient's prognosis. In recent years, the integration of multi-omics technologies has provided unprecedented insights into the systematic analysis of the highly heterogeneous tumor microenvironment at a systemic level. This review begins with a cross-cancer comparison, systematically outlining the functional similarities and differences in key microenvironment components (e.g., tumor-associated macrophages, cancer-associated fibroblasts, osteoclasts, and T cells) in bone metastasis across these three cancer types. It emphasizes how miRNAs mediate intercellular communication via exosomes to coordinately regulate immune evasion, stromal activation, and bone metabolic reprogramming. We further explored the translational potential of miRNA-based liquid biopsies (e.g., miR-141-3p and miR-34a) for diagnosing and prognosticating bone metastasis in breast, prostate, and lung cancers. Finally, this article looks ahead at how integrating multi-omics data with AI predictive models can overcome current delivery and safety challenges, advancing miRNA research towards the ultimate goal of precision medicine.