miR-150 in cancer metastasis: Orchestrating migration, invasion, and angiogenesis through context-dependent mechanisms
Abstract
Metastasis, which accounts for approximately 90 % of cancer-related mortality, is driven by intricate regulatory networks that remain only partially understood. MicroRNA-150 (miR-150) has emerged as a pivotal, context-dependent regulator within these networks, displaying dual functionality as either a tumor suppressor or an oncogene, depending on tumor type, isoform (-5p/-3p), and microenvironmental cues. This comprehensive review synthesizes evidence highlighting miR-150's regulation of critical metastatic processes-namely epithelial-mesenchymal transition, cell migration, invasion, extracellular matrix remodeling, and angiogenesis-through direct targeting of key molecular effectors and its dynamic integration into competitive endogenous RNA (ceRNA) networks involving long non-coding RNAs and circular RNAs. Notably, miR-150 primarily acts as a metastasis suppressor in solid tumors, such as breast, colorectal, and ovarian cancers, by inhibiting pro-metastatic signaling pathways. However, it paradoxically facilitates metastatic progression in specific contexts, including non-small cell lung cancer and cervical carcinoma, by activating oncogenic cascades through suppression of tumor suppressors. Clinically, reduced miR-150 expression serves as a robust indicator of advanced disease stage, lymph node involvement, and poor prognosis, while circulating exosomal miR-150 shows promise as a non-invasive diagnostic biomarker. Therapeutically, tailored strategies employing miR-150 mimics, antagomiRs, or ceRNA-targeted inhibitors hold potential for disrupting metastatic pathways; however, challenges such as isoform-specific targeting, precise delivery, and mitigation of off-target effects remain unresolved. In our view, framing miR-150 as a "double-edged sword" in metastatic regulation provides a conceptual framework for leveraging its molecular versatility to advance precision oncology and mitigate metastatic progression, particularly in combination with emerging systemic therapies.