{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T04:17:22Z","timestamp":1791605842201,"version":"4.3.4"},"reference-count":95,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T00:00:00Z","timestamp":1776816000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Mol. Biosci."],"abstract":"<jats:p>MicroRNAs (miRNAs) are key post-transcriptional regulators that orchestrate complex gene regulatory networks controlling endothelial function, metabolic adaptation, inflammation, and tissue remodeling. Among them, miR-126-3p, miR-126-5p, and miR-423-5p have emerged as context-dependent modulators linking vascular biology with cardiometabolic and oncologic disorders. MiR-126, through its 3p and 5p strands, plays a central role in maintaining endothelial integrity and angiogenic homeostasis. By modulating phosphoinositide 3-kinase\/protein kinase B (PI3K\/AKT), mitogen-activated protein kinase (MAPK), and inflammatory signaling pathways, miR-126 regulates vascular repair, endothelial activation, and immune\u2013vascular interactions. Reduced miR-126 expression is consistently associated with endothelial dysfunction, impaired angiogenic balance, and disease progression in diabetes, chronic kidney disease, and multiple cancers. In parallel, miR-423-5p regulates oxidative stress responses, transforming growth factor beta (TGF-\u03b2)\u2013related pathways, and PI3K\/AKT signaling in a context-dependent manner. Through modulation of redox balance, fibrotic remodeling, and cell survival pathways, miR-423-5p may exert either tumor-suppressive or pro-tumorigenic effects depending on cellular and microenvironmental conditions. In cardiometabolic and renal disorders, it contributes to microvascular dysfunction and inflammatory activation while also demonstrating translational potential as a circulating biomarker candidate. This review synthesizes shared and divergent signaling mechanisms governed by these miRNAs across disease states, emphasizing strand selection, target competition, and network-level cross-talk as determinants of context-specific outcomes. Understanding these multilayered regulatory interactions may support the development of network-oriented biomarker panels and precision RNA-based therapeutic strategies.<\/jats:p>","DOI":"10.3389\/fmolb.2026.1813285","type":"journal-article","created":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T04:34:35Z","timestamp":1776832475000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Translational insights into miR-126 and miR-423: biomarkers and therapeutic targets in cancer, cardiovascular, metabolic and kidney diseases"],"prefix":"10.3389","volume":"13","author":[{"given":"Ma\u0142gorzata","family":"Rodzo\u0144-Norwicz","sequence":"first","affiliation":[{"name":"Clinic of Internal Medicine, Nephrology and Endocrinology with Nuclear Medicine Laboratory and Dialysis Center, State Hospital 2 in Rzesz\u00f3w","place":["Rzesz\u00f3w, Poland"]},{"name":"Department of Human Physiology, Faculty of Medicine, University of Rzesz\u00f3w","place":["Rzesz\u00f3w, Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1350","DOI":"10.1038\/s41416-024-02831-3","article-title":"Circulating miRNA panels as a novel non-invasive diagnostic, prognostic, and potential predictive biomarkers in non-small cell lung cancer (NSCLC)","volume":"131","author":"Abdipourbozorgbaghi","year":"2024","journal-title":"Br. 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