GRWD1 Drives Melanoma Growth Through NF-κB Signaling Pathway

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dc.contributor.authorTurkmen, Dursun
dc.contributor.authorOzbey, Rafet
dc.contributor.authorOzdem, Berna
dc.contributor.authorAlan, Saadet
dc.contributor.authorCetin, Ayten Kilincli
dc.contributor.authorBaran, Fatma Bengisu
dc.contributor.authorDogan, Berat
dc.date.accessioned2026-04-04T13:30:41Z
dc.date.available2026-04-04T13:30:41Z
dc.date.issued2025
dc.departmentİnönü Üniversitesi
dc.description.abstractIntroduction: Melanoma is an aggressive skin cancer with high metastatic potential. The oncogenic protein GRWD1 has been implicated in various cancer types, but its role in melanoma remains unclear. Objectives: To examine the effects of GRWD1 knockdown on melanoma cell proliferation, apoptosis, and migration and to evaluate its prognostic significance in melanoma patients. Methods: A combination of in vitro and clinical analyses was performed. A2058 melanoma cells were treated with GRWD1-specific siRNA, and cell proliferation, apoptosis, and migration assays were conducted. Western blotting was used to assess alterations in key oncogenic pathways. Additionally, clinical tissue samples from melanoma patients were analyzed for GRWD1 expression, and Kaplan-Meier survival analysis was performed to determine its prognostic value. Results: GRWD1 was highly expressed in melanoma cells. GRWD1 knockdown significantly reduced cell proliferation (by 63%), impaired colony formation, and induced apoptosis (cleaved caspase-3 levels increased by 17.3%). Migration capacity decreased by 70%, and NF-kappa B pathway activity was suppressed, leading to reduced expression of Bcl-2, Src, and MDM2, while stabilizing p53. TCGA-based analyses revealed that high GRWD1 expression was significantly associated with shorter survival in metastatic melanoma cases (P=0.00029) but showed no correlation with melanoma subtypes. However, in immunohistochemical analysis of clinical samples, no statistically significant correlation was found between GRWD1 staining intensity and survival. Conclusions: GRWD1 plays a crucial role in melanoma progression by enhancing NF-kappa B activity, promoting proliferation, and suppressing apoptosis. While high GRWD1 expression is associated with poor prognosis in public datasets, further clinical validation with larger patient cohorts is needed to confirm its utility as a prognostic biomarker and therapeutic target.
dc.description.sponsorshipScientific Research Projects Coordination Unit of Inonu University [TCD-2019-2018]
dc.description.sponsorshipThe study was supported by the Scientific Research Projects Coordination Unit of Inonu University with the project code TCD-2019-2018. This study was approved by Clinical Research Ethics Committee of Inonu University Medical Faculty (2022/121) .
dc.identifier.doi10.5826/dpc.1504a5918
dc.identifier.issn2160-9381
dc.identifier.issue4
dc.identifier.orcid0000-0003-0759-5003
dc.identifier.orcid0000-0003-2329-151X
dc.identifier.orcid0000-0001-9076-4669
dc.identifier.orcid0000-0003-4810-1970
dc.identifier.orcid0000-0002-4481-2866
dc.identifier.pmid41236225
dc.identifier.scopus2-s2.0-105026163650
dc.identifier.scopusqualityN/A
dc.identifier.urihttps://doi.org/10.5826/dpc.1504a5918
dc.identifier.urihttps://hdl.handle.net/11616/108291
dc.identifier.volume15
dc.identifier.wosWOS:001614960200012
dc.identifier.wosqualityQ2
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherMattioli 1885
dc.relation.ispartofDermatology Practical & Conceptual
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/openAccess
dc.snmzKA_WOS_20250329
dc.subjectMelanoma
dc.subjectGRWD1
dc.subjectNF-kappa B
dc.subjectTumor progression
dc.subjectSignaling pathway
dc.titleGRWD1 Drives Melanoma Growth Through NF-κB Signaling Pathway
dc.typeArticle

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