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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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