{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T11:07:14Z","timestamp":1782990434711,"version":"3.54.5"},"reference-count":41,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T00:00:00Z","timestamp":1761523200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010355","name":"Hellenic Society of Medical Oncology","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100010355","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>MicroRNAs (miRNAs) are key regulators of gene expression with critical roles in oncogenic signaling. Endometrial cancer (EC) has been redefined with the identification of POLE-ultramutated tumors which, despite their hypermutated phenotype, show more favorable prognosis. We profiled miRNA expression in tumor tissues from forty (40) EC patients and twenty (20) healthy controls using qPCR panels. POLE exonuclease domain mutations (P286R, V411L) were genotyped, and subgroup analyses were conducted between POLE-mutated (n = 7) and POLE-wild-type (n = 33) tumors. Bioinformatic analyses included validated miRNA\u2013mRNA interactions, target enrichment, and Gene Ontology (GO) pathway mapping. Comparison of EC versus healthy endometrium revealed 50 significantly dysregulated (\u2223log2 (FoldReg)\u2223 &gt; 1 and BH FDR &lt; 0.05) miRNAs, including up-regulation of the oncogenic hsa-miR-181a-5p, hsa-miR-23a-3p, hsa-miR-200c-3p, and down-regulation of tumor-suppressive let-7 family members. Target enrichment implicated canonical oncogenic regulators such as MYC, TP53, and VEGFA. POLE-mutated tumor analysis demonstrated a miRNA signature, with 19 miRNAs significantly down-regulated, including let-7f-5p and hsa-miR-200b-3p. Findings for the EC versus healthy endometrium comparison were validated against TCGA-UCEC sequencing data which confirmed concordant dysregulation of key miRNAs across platforms. Our findings reveal that EC is characterized by widespread miRNA deregulation, with a unique global down-regulation signature in POLE-mutated tumors. These results highlight the potential of miRNAs as complementary biomarkers for classification and potential targets in EC.<\/jats:p>","DOI":"10.3390\/ijms262110438","type":"journal-article","created":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T09:16:07Z","timestamp":1761642967000},"page":"10438","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["miRNA Signatures in Endometrial Cancer: Implications for Oncogenesis and Polymerase Epsilon (POLE) Mutation Status"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0783-4847","authenticated-orcid":false,"given":"Alexandros","family":"Lazaridis","sequence":"first","affiliation":[{"name":"2nd Department of Obstetrics and Gynecology, National and Kapodistrian University of Athens, Vasilissis Sofias 76, 11528 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3832-9939","authenticated-orcid":false,"given":"Nikolas","family":"Dovrolis","sequence":"additional","affiliation":[{"name":"Laboratory of Biology, Department of Basic Medical Sciences, Medical School, National and Kapodistrian University of Athens, Michalakopoulou 176, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5741-4288","authenticated-orcid":false,"given":"Hector","family":"Katifelis","sequence":"additional","affiliation":[{"name":"Laboratory of Biology, Department of Basic Medical Sciences, Medical School, National and Kapodistrian University of Athens, Michalakopoulou 176, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Despoina","family":"Myoteri","sequence":"additional","affiliation":[{"name":"Department of Pathology, Aretaieion Hospital, Medical School, National and Kapodistrian University of Athens, 76 Vas. Sofias Avenue, 11528 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iakovos","family":"Vlahos","sequence":"additional","affiliation":[{"name":"Department of Pathology, Aretaieion Hospital, Medical School, National and Kapodistrian University of Athens, 76 Vas. Sofias Avenue, 11528 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8479-6517","authenticated-orcid":false,"given":"Nikos F.","family":"Vlahos","sequence":"additional","affiliation":[{"name":"2nd Department of Obstetrics and Gynecology, National and Kapodistrian University of Athens, Vasilissis Sofias 76, 11528 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3295-6811","authenticated-orcid":false,"given":"Maria","family":"Gazouli","sequence":"additional","affiliation":[{"name":"Laboratory of Biology, Department of Basic Medical Sciences, Medical School, National and Kapodistrian University of Athens, Michalakopoulou 176, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/S0092-8674(04)00045-5","article-title":"MicroRNAs: Genomics, biogenesis, mechanism, and function","volume":"116","author":"Bartel","year":"2004","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1038\/nrc1840","article-title":"Oncomirs\u2014MicroRNAs with a role in cancer","volume":"6","author":"Slack","year":"2006","journal-title":"Nat. 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