Department of Dermatology, Guangzhou First People's Hospital, Guangzhou, Guangdong Province, China.
Department of Dermatology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, China.
Bioengineered. 2022 Mar;13(3):7648-7658. doi: 10.1080/21655979.2022.2050491.
Cancer stem cells (CSCs) are closely related to tumor occurrence, development, metastasis, drug resistance, and recurrence. The role of CSCs in melanoma is poorly understood. Our previous studies suggested that the NOP14 nucleolar protein (NOP14) is involved in melanoma pathogenesis regulation. Importantly, NOP14 overexpression inhibits the Wnt/beta (β)-catenin signaling pathway, an important mechanism regulating CSCs stemness. Therefore, in this study, we aimed to explore the role of NOP14 in the stemness and function of CSCs in melanoma . CD133, a stem cell marker, was used to identify melanoma stem-like cells (SLCs). NOP14 overexpression subsequently decreased the proportion of CD133 SLCs, impaired the colony-forming capabilities, and downregulated the expression of Nanog, SOX2, and OCT4 stem cell markers in A375 and A875 cells, suggesting that NOP14 suppresses the stemness of melanoma SLCs. NOP14 overexpression suppressed the migration, invasion, and angiogenesis-inducing ability of A375-SLCs and A875-SLCs. NOP14 overexpression also inactivated Wnt/β-catenin signaling in melanoma CD133 SLCs. The Wnt signaling activator BML-284 alleviated the effect of NOP14 overexpression on the stemness and function of melanoma CSCs. In conclusion, NOP14 suppresses the stemness and function of melanoma SLCs by inactivating Wnt/β-catenin signaling. Thus, NOP14 is a novel target for CSC treatment in melanoma.: CSCs, cancer stem cells; SLCs, stem-like cells; NOP14, NOP14 nucleolar protein; SCID, severe combined immunodeficiency; β-catenin, beta-catenin; lv-NOP14, lentivirals expressing NOP14; PBS, phosphate buffer saline; HUVECs, human umbilical vein endothelial cells.
癌症干细胞 (CSCs) 与肿瘤的发生、发展、转移、耐药和复发密切相关。CSCs 在黑色素瘤中的作用尚不清楚。我们之前的研究表明，NOP14 核仁蛋白 (NOP14) 参与了黑色素瘤发病机制的调节。重要的是，NOP14 的过表达抑制了 Wnt/β-连环蛋白 (β-catenin) 信号通路，这是调节 CSCs 干性的一个重要机制。因此，在本研究中，我们旨在探讨 NOP14 在黑色素瘤 CSCs 干性和功能中的作用。CD133 是一种干细胞标志物，用于鉴定黑色素瘤干细胞样细胞 (SLCs)。NOP14 的过表达随后降低了 CD133 SLCs 的比例，损害了集落形成能力，并下调了 A375 和 A875 细胞中 Nanog、SOX2 和 OCT4 干细胞标志物的表达，表明 NOP14 抑制了黑色素瘤 SLCs 的干性。NOP14 的过表达抑制了 A375-SLCs 和 A875-SLCs 的迁移、侵袭和血管生成诱导能力。NOP14 的过表达也使黑色素瘤 CD133 SLCs 中的 Wnt/β-catenin 信号失活。Wnt 信号激活剂 BML-284 减轻了 NOP14 过表达对黑色素瘤 CSCs 干性和功能的影响。总之，NOP14 通过使 Wnt/β-catenin 信号失活来抑制黑色素瘤 SLCs 的干性和功能。因此，NOP14 是黑色素瘤 CSC 治疗的一个新靶点。
