{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T17:19:02Z","timestamp":1782235142097,"version":"3.54.5"},"reference-count":58,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2023,2,22]],"date-time":"2023-02-22T00:00:00Z","timestamp":1677024000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fondo Integrativo per la Ricerca (FIR) of the University of Cagliari, Italy"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Pterygium is a multifactorial disease in which UV-B is speculated to play a key role by inducing oxidative stress and phototoxic DNA damage. In search for candidate molecules that are useful for justifying the intense epithelial proliferation observed in pterygium, our attention has been focused on Insulin-like Growth Factor 2 (IGF-2), mainly detected in embryonic and fetal somatic tissues, which regulate metabolic and mitogenic functions. The binding between IGF-2 and its receptor Insulin-like Growth Factor 1 Receptor (IGF-1R) activates the PI3K-AKT pathway, which leads to the regulation of cell growth, differentiation, and the expression of specific genes. Since IGF2 is regulated by parental imprinting, in different human tumors, the IGF2 Loss of Imprinting (LOI) results in IGF-2- and IGF2-derived intronic miR-483 overexpression. Based on these activities, the purpose of this study was to investigate the overexpression of IGF-2, IGF-1R, and miR-483. Using an immunohistochemical approach, we demonstrated an intense colocalized epithelial overexpression of IGF-2 and IGF-1R in most pterygium samples (Fisher\u2019s exact test, p = 0.021). RT-qPCR gene expression analysis confirmed IGF2 upregulation and demonstrated miR-483 expression in pterygium compared to normal conjunctiva (253.2-fold and 12.47-fold, respectively). Therefore, IGF-2\/IGF-1R co-expression could suggest their interplay through the two different paracrine\/autocrine IGF-2 routes for signaling transfer, which would activate the PI3K\/AKT signaling pathway. In this scenario, miR-483 gene family transcription might synergically reinforce IGF-2 oncogenic function through its boosting pro-proliferative and antiapoptotic activity.<\/jats:p>","DOI":"10.3390\/ijms24054329","type":"journal-article","created":{"date-parts":[[2023,2,22]],"date-time":"2023-02-22T03:32:17Z","timestamp":1677036737000},"page":"4329","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Synergic Action of Insulin-like Growth Factor-2 and miRNA-483 in Pterygium Pathogenesis"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3490-1793","authenticated-orcid":false,"given":"Cristina","family":"Maxia","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, University of Cagliari, 09042 Monserrato, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michela","family":"Isola","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Cagliari, 09042 Monserrato, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleonora","family":"Grecu","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Cagliari, 09042 Monserrato, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Cuccu","sequence":"additional","affiliation":[{"name":"Department of Surgical Science, Eye Clinic, Azienda Ospedaliero-Universitaria (AOU), 09123 Cagliari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4385-8002","authenticated-orcid":false,"given":"Alessandra","family":"Scano","sequence":"additional","affiliation":[{"name":"Department of Surgical Sciences, Molecular Biology Service Laboratory, University of Cagliari, 09123 Cagliari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1032-4431","authenticated-orcid":false,"given":"Germano","family":"Orr\u00f9","sequence":"additional","affiliation":[{"name":"Department of Surgical Sciences, Molecular Biology Service Laboratory, University of Cagliari, 09123 Cagliari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nick","family":"Di Girolamo","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Biomedical Sciences, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW 4385, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7247-6994","authenticated-orcid":false,"given":"Andrea","family":"Diana","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Cagliari, 09042 Monserrato, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1357-2492","authenticated-orcid":false,"given":"Daniela","family":"Murtas","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Cagliari, 09042 Monserrato, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1097\/00055735-199908000-00011","article-title":"The pathogenesis of pterygia","volume":"10","author":"Coroneo","year":"1999","journal-title":"Curr. 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