{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T19:34:07Z","timestamp":1786649647882,"version":"build-2736575974"},"reference-count":49,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","license":[{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"abstract":"\n Background:<\/jats:title>\n \n Approximately 10%\u201315% of all breast cancer diagnoses are identified as triple-negative breast cancer (TNBC), a subtype known for its poor prognosis due to chemoresistance. TNBC lacks any receptors or proteins that are overexpressed, thus lacking targeted therapy. The protein\n LGR5<\/jats:italic>\n , a marker for cancer stem cells and a promoter of Wnt signaling pathway activity, is notably upregulated in TNBC cases.\n LGR5<\/jats:italic>\n plays an important role in chemoresistance and tumorigenesis. Considering this, our research aim was to investigate the effect of\n LGR5<\/jats:italic>\n suppression by using specific siRNA in multicellular spheroid of the TNBC cell line and evaluation of stemness-related gene expression changes.\n <\/jats:p>\n <\/jats:sec>\n \n Materials and Methods:<\/jats:title>\n Multicellular spheroids of the MDA-MB-231 TNBC cell line were prepared. The exosome was extracted from the human adipose mesenchymal stem cells (ADMSCs) and confirmed. Multicellular spheroids were separately transfected with siRNA, EXO-siRNA and, treated with cisplatin alone. Gene expression was studied using qRT-PCR.<\/jats:p>\n <\/jats:sec>\n \n Results:<\/jats:title>\n \n Our findings revealed that inhibiting\n LGR5<\/jats:italic>\n with siRNA significantly reduces\n LGR5<\/jats:italic>\n expression. Furthermore, the results indicated a notable increase in the expression of stemness markers (\n SOX9<\/jats:italic>\n ,\n OCT4<\/jats:italic>\n , and\n NANOG<\/jats:italic>\n ) in samples treated with cisplatin. However, the reduction of\n LGR5<\/jats:italic>\n expression via siRNA led to a marked decrease in\n SOX9<\/jats:italic>\n and\n OCT4<\/jats:italic>\n levels, while\n NANOG<\/jats:italic>\n expression remained largely unchanged.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions:<\/jats:title>\n \n In summary, the results indicated that\n LGR5<\/jats:italic>\n suppression is effective in reducing stemness-related genes and may be considered a good candidate for combination therapy along with chemotherapy.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.4103\/abr.abr_124_24","type":"journal-article","created":{"date-parts":[[2025,12,30]],"date-time":"2025-12-30T14:00:29Z","timestamp":1767103229000},"update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":0,"title":["Effect of siRNA-mediated LGR5 Inhibition on the Expression of Stemness-related Genes in Triple-negative Breast Cancer Spheroid Model"],"prefix":"10.4103","volume":"14","author":[{"given":"Sepideh","family":"Ghobakhloo","sequence":"first","affiliation":[{"name":"Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran"},{"name":"Pediatric Inherited Diseases Research Center, Research Institute for Primordial Prevention of Non-Communicable Diseases, Isfahan University of Medical Sciences, Isfahan, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sima","family":"Jafarpour","sequence":"additional","affiliation":[{"name":"Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran"},{"name":"Pediatric Inherited Diseases Research Center, Research Institute for Primordial Prevention of Non-Communicable Diseases, Isfahan University of Medical Sciences, Isfahan, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reza","family":"Nedaeinia","sequence":"additional","affiliation":[{"name":"Pediatric Inherited Diseases Research Center, Research Institute for Primordial Prevention of Non-Communicable Diseases, Isfahan University of Medical Sciences, Isfahan, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rasoul","family":"Salehi","sequence":"additional","affiliation":[{"name":"Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran"},{"name":"Pediatric Inherited Diseases Research Center, Research Institute for Primordial Prevention of Non-Communicable Diseases, Isfahan University of Medical Sciences, Isfahan, 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