Targeting Spatiotemporal Heterogeneity of oncomiRNAs: A New Frontier in Cancer Therapy.

Abstract

miRNAs are short RNA transcripts that modulate gene expression after transcription and have emerged as pivotal regulators of cancer biology. A subset, termed oncomiRNAs, functions as oncogenes or tumor suppressors, influencing key cellular events such as cell growth, programmed cell death, neovascularization, tissue invasion, and metastatic spread. Dysregulation of these miRNAs drives tumor initiation and progression, underscoring their role in cancer evolution. Traditionally, studies have relied on bulk tissue analyses, overlooking the profound spatiotemporal heterogeneity of oncomiRNA expression, including variations across tumor regions, metastatic sites, disease stages, and during treatment. Advances in spatial transcriptomics, single-cell profiling, and longitudinal liquid biopsy technologies have provided new insights into the dynamic regulation of oncomiRNAs. These approaches reveal significant spatiotemporal variability in miRNA expression and are increasingly implicated in shaping tumor heterogeneity, therapeutic resistance, immune evasion, and divergent clinical outcomes. Emerging evidence underscores the importance of integrating these dynamic molecular patterns into biomarker discovery frameworks and precision oncology strategies. Furthermore, the incorporation of artificial intelligence and multi-omics data integration is enhancing patient stratification and predictive modeling. A comprehensive understanding of the spatiotemporal regulation of oncomiRNAs is essential for advancing next-generation cancer diagnostics and therapeutics. Future efforts should focus on systematic multi-region and longitudinal study designs, as well as their integration into adaptive clinical trials. Leveraging these insights may enable miRNA-guided, stage-adapted precision cancer theranostics in heterogeneous malignancies.