{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T04:30:41Z","timestamp":1791865841084,"version":"4.3.4"},"reference-count":37,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,4,14]],"date-time":"2021-04-14T00:00:00Z","timestamp":1618358400000},"content-version":"vor","delay-in-days":103,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2016\/15831-3"],"award-info":[{"award-number":["2016\/15831-3"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["BioMed Research International"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:p>New prevention strategies are needed to detect cervical intraepithelial neoplasia (CIN). The microRNA expression analysis has already been reported as molecular biomarkers in the early detection of cervical cancer (CC) through minimally invasive samples, such as liquid biopsy, obtained through collection using liquid\u2010based cytology (LBC). In this study, we aimed to identify molecular signatures of microRNAs in cervical precursor lesions from LBC cervical and the molecular pathways potentially associated with the CC progression. We analyzed 31 LBC cervical samples from women who underwent colposcopy. These samples were divided into two groups: the first group was composed of samples without precursor lesions of CC, considering the control group, referred to as healthy female subjects (HFS; <jats:italic>n<\/jats:italic> = 11). The second group corresponded to women diagnosed with cervical interepithelial neoplasia grade 3 (CIN 3; <jats:italic>n<\/jats:italic> = 20). We performed microRNA and gene expression profiling using the nCounter\u00ae miRNA Expression Assays (NanoString Technology) and PanCancer Pathways (NanoString Technology), respectively. A microRNA target prediction was performed by mirDIP, and molecular pathway interaction was constructed using Cytoscape. Bidirectional in silico analyses and Pearson\u2019s correlation were performed for associated the relation between genes, and miRNAs differentially expressed related cervical cancer progression were performed. We found that the expression of nine microRNAs was significantly higher, two were downregulated (miR\u2010381\u20103p and miR\u20104531), and seven miRNAs were upregulated (miR\u2010205\u20105p, miR\u2010130a\u20103p, miR\u20103136\u20103p, miR\u2010128\u20102\u20105p, let\u20107f\u20105p, miR\u2010202\u20103p, and miR\u2010323a\u20105p) in CIN 3 (fold\u2009change \u2265 2 and <jats:italic>p<\/jats:italic> \u2264 0.05). The miRNA expression patterns were independent of hr\u2010HPV infection. We identified four miRNAs (miR\u2010205\u20105p, miR\u2010130a\u20103p, miR\u20104531, and miR\u2010381\u20103p) that could be used as biomarkers for CIN 3 in LBC samples through multiple logistic regression analyses. We found 16 genes differentially expressed between CIN 3 and HSF samples (fold\u2009change \u2265 2 and <jats:italic>p<\/jats:italic> \u2264 0.05). We found the correlation between miR\u2010130a\u20103p and CCND1(<jats:italic>R<\/jats:italic> = \u22120.52; <jats:italic>p<\/jats:italic> = 0.0029), miR\u2010205\u20105p and EGFR (<jats:italic>R<\/jats:italic> = 0.53; <jats:italic>p<\/jats:italic> = 0.0021), and miR\u20104531 and SMAD2 (<jats:italic>R<\/jats:italic> = \u22120.54; <jats:italic>p<\/jats:italic> = 0.0016). In addition, we demonstrated the most significant pathways of the targets associated with cervical cancer progression (FDR\u2010corrected <jats:italic>p<\/jats:italic> &lt; 0.001). This study demonstrated that miRNA biomarkers may distinguish healthy cervix and CIN 3 and regulate important molecular pathways of carcinogenesis.<\/jats:p>","DOI":"10.1155\/2021\/6650966","type":"journal-article","created":{"date-parts":[[2021,4,14]],"date-time":"2021-04-14T20:49:54Z","timestamp":1618433394000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["MicroRNA Biomarkers of High\u2010Grade Cervical Intraepithelial Neoplasia in Liquid Biopsy"],"prefix":"10.1155","volume":"2021","author":[{"given":"Rhafaela L.","family":"Causin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luciane S.","family":"da Silva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriane F.","family":"Evangelista","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Let\u00edcia F.","family":"Leal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen C. 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