{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T12:00:48Z","timestamp":1789214448975,"version":"build-2803163510"},"reference-count":50,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,1,16]],"date-time":"2023-01-16T00:00:00Z","timestamp":1673827200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100011892","name":"Kaohsiung Chang Gung Memorial Hospital, Chang Gung Medical Foundation","doi-asserted-by":"publisher","award":["CMRPG8H0471"],"award-info":[{"award-number":["CMRPG8H0471"]}],"id":[{"id":"10.13039\/501100011892","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011892","name":"Kaohsiung Chang Gung Memorial Hospital, Chang Gung Medical Foundation","doi-asserted-by":"publisher","award":["CMRPG8H0472"],"award-info":[{"award-number":["CMRPG8H0472"]}],"id":[{"id":"10.13039\/501100011892","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011892","name":"Kaohsiung Chang Gung Memorial Hospital, Chang Gung Medical Foundation","doi-asserted-by":"publisher","award":["EDAHT108033"],"award-info":[{"award-number":["EDAHT108033"]}],"id":[{"id":"10.13039\/501100011892","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004738","name":"E-Da Hospital","doi-asserted-by":"publisher","award":["CMRPG8H0471"],"award-info":[{"award-number":["CMRPG8H0471"]}],"id":[{"id":"10.13039\/501100004738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004738","name":"E-Da Hospital","doi-asserted-by":"publisher","award":["CMRPG8H0472"],"award-info":[{"award-number":["CMRPG8H0472"]}],"id":[{"id":"10.13039\/501100004738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004738","name":"E-Da Hospital","doi-asserted-by":"publisher","award":["EDAHT108033"],"award-info":[{"award-number":["EDAHT108033"]}],"id":[{"id":"10.13039\/501100004738","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Upper tract urothelial cancer (UTUC) is a less common disease in Western countries but has a high level of prevalence in Asian populations. Compared to bladder cancer, unique etiologic and genomic factors are involved in UTUC. Fibroblast growth factor receptor 3 (FGFR3) up-regulation has been proposed as a promising target for bladder cancer therapy. In this study, we aimed to profile the expression of FGFR3 in Asian and Caucasian UTUC tissues and to evaluate the in vitro therapeutic efficacy of small interference RNA (siRNA)-mediated FGFR3 silencing in UTUC treatment. The FGFR3 expression levels in renal pelvis tissues and microarray sections from Asian and Caucasian patients with UTUC, respectively, were measured via immunohistochemistry. The BFTC-909 and UM-UC-14 UTUC cell lines were used to examine the effects of FGFR3 silencing on proliferation, migration, epithelial\u2013mesenchymal transition (EMT) marker expression, and signaling machinery. FGFR3 expression increased as the TNM stage increased in both Asian and Caucasian UTUC tumors, and no statistical difference was identified between the two groups. In vitro studies demonstrated that FGFR3 siRNA delivery significantly inhibited proliferation and migration and suppressed the expression of EMT markers and transcription factors in UTUC cells. Mechanistically, FGFR3 silencing alleviated the constitutive expression of RAS and the phosphorylation of MAPK signaling mediators, including ERK1\/2 and JNK1\/2. FGFR3 silencing elicited an apoptosis-inducing effect similar to that of FGFR inhibition. Conclusion: siRNA-targeted FGFR3 expression may impede the expansion and invasion of UTUC cells by alleviating the RAS\/MAPK signaling pathway. The genetic interference of FGFR3 expression via siRNA in UTUC cells may constitute a useful therapeutic strategy.<\/jats:p>","DOI":"10.3390\/ijms24021776","type":"journal-article","created":{"date-parts":[[2023,1,16]],"date-time":"2023-01-16T05:30:07Z","timestamp":1673847007000},"page":"1776","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Genetic Interference of FGFR3 Impedes Invasion of Upper Tract Urothelial Carcinoma Cells by Alleviating RAS\/MAPK Signal Activity"],"prefix":"10.3390","volume":"24","author":[{"given":"Gong-Kai","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Pathology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2794-4960","authenticated-orcid":false,"given":"Chao-Cheng","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Pathology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan"},{"name":"Biobank and Tissue Bank, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chih-Hsiung","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Urology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan-Tso","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Urology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Po-Ching","family":"Tsai","sequence":"additional","affiliation":[{"name":"Department of Pathology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7803-9384","authenticated-orcid":false,"given":"Ying-Hsien","family":"Kao","sequence":"additional","affiliation":[{"name":"Department of Medical Research, E-Da Hospital, I-Shou University, Kaohsiung 82445, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yueh-Hua","family":"Chung","sequence":"additional","affiliation":[{"name":"Department of Urology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan"},{"name":"Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1111\/j.1442-2042.2006.01429.x","article-title":"High incidence of and risk factors for metachronous bilateral upper tract urothelial carcinoma in Taiwan","volume":"13","author":"Huang","year":"2006","journal-title":"Int. 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