{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T04:59:51Z","timestamp":1785214791507,"version":"3.55.0"},"reference-count":52,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T00:00:00Z","timestamp":1784937600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100019346","name":"Instituto Nacional de Cancerolog\u00eda","doi-asserted-by":"crossref","award":["C19010300427"],"award-info":[{"award-number":["C19010300427"]}],"id":[{"id":"10.13039\/100019346","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Field cancerization describes molecular alterations occurring in histologically normal tissues surrounding tumors that may contribute to cancer initiation and progression. In prostate cancer (PCa), the molecular characteristics of peritumoral tissue (PTT) remain incompletely understood. Because microRNAs (miRNAs) play key roles in gene regulation, tumor progression, and microenvironmental remodeling, we investigated miRNA expression patterns and regulatory networks across benign tissue (BT), PTT, and tumor tissue (TT). Small RNA sequencing was performed on matched formalin-fixed paraffin-embedded samples from 40 patients with PCa. Differential expression analysis was conducted using DESeq2, adjusting for age and Gleason grade, while functional enrichment analysis and weighted gene co-expression network analysis (WGCNA) were used to identify dysregulated pathways and conserved miRNA modules. PTT exhibited a molecular profile intermediate between BT and TT, consistent with a field cancerization effect. Compared with BT, 102 miRNAs were differentially expressed in TT and 57 in PTT, with 39 miRNAs (68% of the PTT-associated miRNAs) overlapping the tumor signature. Shared dysregulated pathways included PI3K\u2013Akt, p53, and HIF-1 signaling; whereas, PTT showed additional enrichment in pathways related to epigenetic regulation (Polycomb Repressive Complex) and cellular stress responses (mitophagy, protein processing in ER) exclusively through up-regulated miRNAs; no pathways were uniquely enriched from down-regulated miRNAs in PTT. WGCNA identified conserved miRNA modules enriched for members of the let-7, miR-200, miR-103\/107, and miR-106a~363 families, which have established roles in epithelial\u2013mesenchymal transition, tumor progression, and microenvironmental remodeling. Collectively, these findings demonstrate that histologically benign peritumoral tissues harbor tumor-associated miRNA programs and regulatory networks that closely resemble those observed in prostate tumors, providing molecular evidence of field cancerization in PCa and identifying potential miRNA-mediated mechanisms relevant to disease progression and biomarker development.<\/jats:p>","DOI":"10.3390\/ijms27156637","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T09:47:41Z","timestamp":1785145661000},"page":"6637","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrated miRNA Sequencing and Network Analysis Reveal a Molecular Continuum Between Peritumoral and Tumor Tissue in Prostate Cancer"],"prefix":"10.3390","volume":"27","author":[{"given":"Rafael","family":"Parra-Medina","sequence":"first","affiliation":[{"name":"Pathology Department, Instituto Nacional de Cancerolog\u00eda (INC), Bogota 111511, Colombia"},{"name":"Research Institute, Universidad FUCS, Bogot\u00e1 111221, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4007-1711","authenticated-orcid":false,"given":"Elizabeth","family":"Vargas-Castellanos","sequence":"additional","affiliation":[{"name":"Hospital Universitario Mayor\u2014M\u00e9deri, Universidad del Rosario, Bogota 110321, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9511-8583","authenticated-orcid":false,"given":"Dayana","family":"Rodr\u00edguez-Morales","sequence":"additional","affiliation":[{"name":"Pathology Department, Instituto Nacional de Cancerolog\u00eda (INC), Bogota 111511, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Ram\u00edrez-Clavijo","sequence":"additional","affiliation":[{"name":"Department of Biology, Faculty of Natural Sciences, Universidad del Rosario, Bogota 111221, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5961-6761","authenticated-orcid":false,"given":"Jovanny","family":"Zabaleta","sequence":"additional","affiliation":[{"name":"Department of Interdisciplinary Oncology, Louisiana State University Health Science Center (LSUHSC), New Orleans, LA 70112, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0633-1332","authenticated-orcid":false,"given":"C\u00e9sar","family":"Pay\u00e1n-G\u00f3mez","sequence":"additional","affiliation":[{"name":"Direcci\u00f3n Acad\u00e9mica, Universidad Nacional de Colombia, Sede de La Paz, La Paz 201501, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,25]]},"reference":[{"key":"ref_1","first-page":"229","article-title":"Global Cancer Statistics 2022: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. 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