Please use this identifier to cite or link to this item: https://hdl.handle.net/11147/15578
Title: Modulating Cancer Stem Cell Characteristics in CD133+ Melanoma Cells through Hif1α, KLF4, and SHH Silencing
Authors: Ozdil, Berrin
Avci, Cigir Biray
Calik-Kocaturk, Duygu
Gorgulu, Volkan
Uysal, Aysegul
Guler, Gunnur
Aktug, Huseyin
Publisher: Amer Chemical Soc
Abstract: Malignant melanoma is a highly aggressive form of skin cancer, partly driven by a subset of cancer stem cells (CSCs) with remarkable capacities for self-renewal, differentiation, and resistance to therapy. In this study, we examined how silencing three key genes-Hif1 alpha, KLF4, and SHH-affects CSC characteristics. Using small interfering RNA (siRNA)-based approaches, we observed significant changes at both the gene and protein levels, shedding light on how these pathways influence melanoma progression. Our results demonstrated that silencing these genes reduces the stem-like features of CSCs. Notably, Hif1 alpha silencing triggered a marked decrease in hypoxia-related gene expression, while targeting SHH led to a reduction in Gli1, a downstream effector of SHH signaling, highlighting its potential as a therapeutic target. We also observed changes in epigenetic markers such as HDAC9 and EP300, which play crucial roles in maintaining stemness and regulating gene expression. Interestingly, these interventions appeared to reprogram CSCs, pushing them toward a phenotype distinct from both traditional CSCs and non-stem cancer cells (NCSCs). Our findings emphasize the importance of targeting key signaling pathways in melanoma CSCs and underscore the value of mimicking the tumor microenvironment in experimental models. By revealing the dynamic plasticity of melanoma CSCs, this study offers fresh insights into potential therapeutic strategies, particularly using siRNA to modulate pathways associated with tumor progression and stem cell behavior.
URI: https://doi.org/10.1021/acsomega.5c00799
ISSN: 2470-1343
Appears in Collections:PubMed İndeksli Yayınlar Koleksiyonu / PubMed Indexed Publications Collection
Scopus İndeksli Yayınlar Koleksiyonu / Scopus Indexed Publications Collection
WoS İndeksli Yayınlar Koleksiyonu / WoS Indexed Publications Collection

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