Publication: miR-106b-5p as a Central Regulator of Cancer Progression and Chemotherapy-Induced Cardiotoxicity: From Molecular Mechanisms to Clinical Translation
Authors
Miriam Ruiz Ballester ; Francisco Jose Bastida Nicolas ; Fernando Soler Pardo ; Jose Luis Alonso Romero ; Cesar Caro Martínez ; Domingo Pascual Figal ; Antonio Lax ; Maria del Carmen Asensio Lopez
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DOI
https://doi.org/10.3390/ijms262010002
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info:eu-repo/semantics/article
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Abstract
MicroRNAs (miRNAs) are critical regulators of gene expression in cancer biology and cardiovascular disease. miR-106b-5p, a member of the miR-106b-25 cluster, has been widely studied for its oncogenic activity in various malignancies. However, its role as a direct molecular driver of anthracycline-induced cardiotoxicity has only recently been uncovered. This finding highlights new therapeutic possibilities at the intersection of oncology and cardiovascular medicine. This review outlines the dual role of miR-106b-5p as a key modulator in both tumor progression and chemotherapy-induced cardiac dysfunction. miR-106b-5p is upregulated in numerous cancers—including breast, prostate, lung, gastric, colorectal, hepatocellular, and esophageal—and promotes tumorigenesis via suppression of tumor suppressors such as PTEN, BTG3, p21, and SMAD7, leading to activation of oncogenic pathways like PI3K/AKT and TGF-β. Importantly, we present the first evidence that miR-106b-5p is significantly upregulated in the myocardium in response to doxorubicin treatment, where it drives left ventricular dysfunction by targeting PR55α, a key regulator of PP2A activity. This pathway results in cytoplasmic HDAC4 accumulation, aberrant activation of the YY1 transcription factor, and upregulation of sST2, a biomarker linked to adverse cardiac remodeling and poor prognosis. In response, we developed AM106, a novel locked nucleic acid antagomir that silences miR-106 b-5p. Preclinical studies demonstrate that AM106 restores PR55α/PP2A activity, reduces sST2 expression, and prevents structural and functional cardiac damage without compromising anti-tumor efficacy. In parallel, artificial intelligence (AI) tools could be leveraged in the future—based on established AI applications in miRNA cancer research—to accelerate the identification of miR-106b-5p-related biomarkers and guide personalized therapy selection. Our findings position miR-106b-5p as a previously unrecognized molecular bridge between cancer and doxorubicin-induced cardiotoxicity. The development of the AM106 antagomir represents a promising approach with potential clinical applicability in cardio-oncology, offering dual benefits: tumor control and cardioprotection. Coupling this innovation with AI-driven analysis of patient data may enable precision risk stratification, early intervention, and improved outcomes. miR-106b-5p thus emerges as a central therapeutic target and biomarker candidate for transforming the clinical management of cancer patients at risk for heart failure.
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Citation
Asensio Lopez, M. D. C., Ruiz Ballester, M., Bastida Nicolas, F. J., Soler Pardo, F., Alonso-Romero, J. L., Caro-Martinez, C., ... & Lax, A. (2025). miR-106b-5p as a Central Regulator of Cancer Progression and Chemotherapy-Induced Cardiotoxicity: From Molecular Mechanisms to Clinical Translation. International Journal of Molecular Sciences, 26(20), 10002.
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