MicroRNAs: Dual-Edged Cancer Biomarkers Revolutionizing Early Detection and Staging

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Abstract

Background: microRNAs (miRNAs) are small, non-coding RNAs that regulate gene expression post-transcriptionally and are now recognized as central players in tumorigenesis, progression, and therapeutic resistance. Their remarkable stability in body fluids and close integration with oncogenic and tumor-suppressive pathways have positioned miRNAs as promising diagnostic, prognostic, and therapeutic biomarkers across diverse cancers. However, the dual and context-dependent nature of many miRNAs, together with methodological heterogeneity, complicates their translation into routine clinical practice.Methods: A comprehensive literature review was conducted using PubMed/MEDLINE, Embase, and Web of Science from 1993 to June 2025 to identify peer-reviewed studies evaluating miRNAs in human cancers. Articles were included if they investigated miRNAs in relation to cancer biology, biomarker potential (diagnostic, prognostic, or predictive), metastasis and EMT, the tumor microenvironment, or therapeutic modulation. Mechanistic, translational, and clinical studies were all considered. Data were extracted on cancer type, sample source, miRNAs studied, assay methods, clinical associations, and functional validation. Due to heterogeneity in design and reporting, a narrative thematic synthesis was undertaken rather than meta-analysis.Results: Evidence across multiple malignancies shows that specific miRNAs function as oncomiRs, promoting proliferation, survival, angiogenesis, immune evasion, and metastasis (for example, miR-21, miR-155, miR-10b, and the miR-17-92 cluster), while others act as tumor-suppressor miRNAs, constraining oncogenic signalling, cell-cycle progression, and metastatic spread (for example, miR-34a, miR-126, miR-145, miR-124, miR-15a/16-1, and the miR-200 family). Distinct expression signatures have been associated with early-stage disease, advanced stage, and metastatic patterns in solid tumors and hematological malignancies. Circulating and exosomal miRNAs show high stability and have demonstrated potential for non-invasive cancer detection, risk stratification, and monitoring of treatment response. Several miRNAs correlate with survival outcomes and resistance to chemotherapy, targeted agents, and immunotherapies. Preclinical models support miRNA-based therapies, including mimics to restore tumor-suppressor miRNAs and inhibitors (antagomirs) to silence oncomiRs, with emerging delivery platforms such as nanoparticles and engineered exosomes.Conclusion: microRNAs (miRNAs) emerge as integrative cancer biomarkers that reflect underlying genetic, epigenetic, and microenvironmental complexity. Current evidence indicates their potential to improve early detection, refine prognostic stratification, and inform therapeutic decision-making. However, heterogeneity in analytical methods, reference standards, and study design, together with the dual and context-dependent functions of individual miRNAs, limits comparability and hinders routine clinical adoption. Progress will depend on rigorous assay standardization, harmonized reporting, and validation of candidate miRNAs and panels in large, prospective, multi-centre cohorts. Integrating miRNA profiles with other molecular and clinical data, and advancing safe, effective miRNA-based therapeutics, will be essential to translate this promising biomarker class into tangible benefits for patients.

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