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Immunol."],"abstract":"<jats:p>Preterm birth (PTB) remains the leading cause of neonatal mortality and long-term complications worldwide, yet its molecular pathogenesis\u2014particularly the coordinated regulation across different gestational tissues\u2014is poorly understood. MicroRNAs (miRNAs) are key regulators of gene expression and exhibit tissue-specific patterns in pregnancy-related tissues, including the cervix, placenta, and amniotic membrane. This narrative review provides a comprehensive and integrative overview from a perspective of putative cross-tissue miRNA crosstalk. We summarize the differential miRNA expression profiles across gestational tissues and their associations with PTB, the tissue-specific mechanisms by which miRNAs regulate inflammatory responses, extracellular matrix remodeling, apoptosis, and barrier disruption, as well as the synergistic effects of multi-tissue-derived miRNAs and their potential as predictive biomarkers. We also evaluate the current status of miRNA-based therapeutic strategies. Our overview reveals that miRNA mimics (e.g., miR-21-5p, miR-199a-3p) and antagonists hold preclinical therapeutic potential in modulating inflammatory cascades and preserving cervical barrier function. However, clinical translation faces three major bottlenecks: the lack of pregnancy-specific delivery systems, safety concerns arising from the multi-target nature of miRNAs, and the challenge of targeting multi-tissue synergistic pathological changes with single-agent interventions. Emerging strategies\u2014including exosome-based delivery, ligand-modified nanocarriers, and combination therapies\u2014are currently being explored. The multi-tissue miRNA framework proposed in this review integrates miRNA biomarkers for early risk stratification with targeted therapeutic interventions, providing a new theoretical foundation for research directions in personalized risk assessment and targeted intervention strategies for PTB.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1948569","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T11:31:02Z","timestamp":1790076662000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Multi-tissue miRNA networks in preterm birth: from molecular mechanisms to precision medicine"],"prefix":"10.3389","volume":"17","author":[{"given":"Pei","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Gynecology and Obstetrics, The First Affiliated Hospital (Southwest Hospital) of Army Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, The First Affiliated Hospital (Southwest Hospital) of Army Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, The First Affiliated Hospital (Southwest Hospital) of Army Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shicang","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Stem Cell and Regenerative Medicine, Institute of Pathology and Southwest Cancer Center, The First Affiliated Hospital (Southwest Hospital) of Army Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, The First Affiliated Hospital (Southwest Hospital) of Army Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1003","DOI":"10.1038\/s41598-022-04881-0","article-title":"Genome and transcriptome profiling of spontaneous preterm birth phenotypes","volume":"12","author":"Gupta","year":"2022","journal-title":"Sci Rep"},{"key":"B2","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1186\/s12884-020-02940-w","article-title":"The association between parity and spontaneous preterm birth: a population based study","volume":"20","author":"Koullali","year":"2020","journal-title":"BMC Pregnancy Childbirth"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0265853","article-title":"Is there a maternal blood biomarker that can predict spontaneous preterm birth prior to labour onset? 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