{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T09:56:57Z","timestamp":1771927017536,"version":"3.50.1"},"reference-count":27,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T00:00:00Z","timestamp":1771286400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>This study aimed to evaluate the mRNA and protein levels of SMURF1 and SMURF2 in breast cancer and to elucidate their potential biological roles through in silico analyses. Tumor and adjacent normal tissue samples were collected from 30 newly diagnosed breast cancer patients who underwent mastectomy. The mRNA expression levels of SMURF1 and SMURF2 were analyzed by quantitative PCR (qPCR), and their protein expression patterns were evaluated using immunohistochemistry (IHC). In addition, protein\u2013protein interaction (PPI) and functional enrichment analyses were performed via the STRING database to identify potential molecular interactions and biological pathways associated with these genes. The mRNA expression level of SMURF1 was significantly downregulated in tumor tissues compared to normal breast tissues (p = 0.002), whereas no significant difference was observed in SMURF2 mRNA expression (p = 0.981). IHC results revealed that SMURF1 and SMURF2 protein levels did not differ significantly between tumor and normal samples. The in silico analysis demonstrated that SMURF1 and SMURF2 interact with multiple proteins involved in key signaling pathways, particularly the TGF-\u03b2\/BMP and Wnt\/\u03b2-catenin pathways. The findings suggest that the downregulation of SMURF1 in breast cancer may contribute to tumor progression by enhancing Wnt\/\u03b2-catenin signaling activity. The interactions of SMURF1 and SMURF2 with TGF-\u03b2\/BMP pathway regulators indicate that these genes may play dual roles in both tumor-suppressive and oncogenic mechanisms, depending on the cellular context.<\/jats:p>","DOI":"10.3390\/ijms27041921","type":"journal-article","created":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T13:15:35Z","timestamp":1771334135000},"page":"1921","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["SMURF1 Downregulation Highlights Its Potential Role in Breast Cancer"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1172-5536","authenticated-orcid":false,"given":"Leyla","family":"Tekin","sequence":"first","affiliation":[{"name":"Department of Pathology, Faculty of Medicine, Mu\u011fla S\u0131tk\u0131 Ko\u00e7man University, Mu\u011fla 48000, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3979-4413","authenticated-orcid":false,"given":"Funda","family":"Din\u00e7","sequence":"additional","affiliation":[{"name":"Department of Radiology, Faculty of Medicine, Mu\u011fla S\u0131tk\u0131 Ko\u00e7man University, Mu\u011fla 48000, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4252-8490","authenticated-orcid":false,"given":"Cenk","family":"Yazkan","sequence":"additional","affiliation":[{"name":"Department of Surgical Medical Sciences, Faculty of Medicine, Mu\u011fla S\u0131tk\u0131 Ko\u00e7man University, Mu\u011fla 48000, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-6517-4522","authenticated-orcid":false,"given":"Murat","family":"Cenik","sequence":"additional","affiliation":[{"name":"Department of Medical Biology, Institute of Health Sciences, Mu\u011fla S\u0131tk\u0131 Ko\u00e7man University, Mu\u011fla 48000, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3821-3621","authenticated-orcid":false,"given":"\u00c7ilem","family":"\u00d6zdemir","sequence":"additional","affiliation":[{"name":"Department of Bioinformatics, Graduate School of Natural and Applied Sciences, Mu\u011fla S\u0131tk\u0131 Ko\u00e7man University, Mu\u011fla 48000, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3729-3225","authenticated-orcid":false,"given":"Onur","family":"Ama\u00e7","sequence":"additional","affiliation":[{"name":"Department of Pathology, Faculty of Medicine, Mu\u011fla S\u0131tk\u0131 Ko\u00e7man University, Mu\u011fla 48000, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9300-9324","authenticated-orcid":false,"given":"Tuba","family":"Edg\u00fcnl\u00fc","sequence":"additional","affiliation":[{"name":"Department of Medical Biology, Faculty of Medicine, Mu\u011fla S\u0131tk\u0131 Ko\u00e7man University, Mu\u011fla 48000, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,17]]},"reference":[{"key":"ref_1","first-page":"6116","article-title":"The 630-kb Lung Cancer Homozygous Deletion Region on Human Chromosome 3p21.3: Identification and Evaluation of the Resident Candidate Tumor Suppressor Genes","volume":"60","author":"Lerman","year":"2000","journal-title":"Cancer Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1186\/bcr42","article-title":"Transforming growth factor-\u03b2 and breast cancer: Transforming growth factor-\u03b2\/SMAD signaling defects and cancer","volume":"2","author":"Kretzschmar","year":"2000","journal-title":"Breast Cancer Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.trecan.2016.11.008","article-title":"Targeting TGF-\u03b2 Signaling in Cancer","volume":"3","author":"Colak","year":"2017","journal-title":"Trends Cancer"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1038\/cr.2008.302","article-title":"Signaling cross-talk between TGF-\u03b2\/BMP and other pathways","volume":"19","author":"Guo","year":"2009","journal-title":"Cell Res."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Koganti, P., Levy-Cohen, G., and Blank, M. 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