Modulating Cancer Stem Cell Characteristics in CD133+ Melanoma Cells through Hif1α, KLF4, and SHH Silencing
Makaleler > Tam Makale · 2025
Yazarlar: Berrin Özdil Bay, Çığır BİRAY AVCI, Duygu Kocatürk, Volkan Görgülü, Ayşegül UYSAL, Günnur Güler, Nefise Ülkü KARABAY YAVAŞOĞLU, Hüseyin AKTUĞ
ACS OMEGA, SCI Expanded İndekslerine Giren Dergi, Uluslararası, Wos, 2025, cilt xx, ss xx-xx
Özet
<p>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 threekey genes�Hif1α, KLF4, and SHH�affects CSC characteristics. Using small interfering RNA (siRNA)-based approaches, weobserved significant changes at both the gene and protein levels, shedding light on how these pathways influence melanomaprogression. Our results demonstrated that silencing these genes reduces the stem-like features of CSCs. Notably, Hif1α silencingtriggered a marked decrease in hypoxia-related gene expression, while targeting SHH led to a reduction in Gli1, a downstreameffector of SHH signaling, highlighting its potential as a therapeutic target. We also observed changes in epigenetic markers such asHDAC9 and EP300, which play crucial roles in maintaining stemness and regulating gene expression. Interestingly, theseinterventions appeared to reprogram CSCs, pushing them toward a phenotype distinct from both traditional CSCs and non-stemcancer cells (NCSCs). Our findings emphasize the importance of targeting key signaling pathways in melanoma CSCs andunderscore the value of mimicking the tumor microenvironment in experimental models. By revealing the dynamic plasticity ofmelanoma CSCs, this study offers fresh insights into potential therapeutic strategies, particularly using siRNA to modulate pathwaysassociated with tumor progression and stem cell behavior.</p>