The NOP14 nucleolar protein suppresses the function and stemness of melanoma stem-like cells through Wnt/beta-catenin signaling inactivation

• Published in: Bioengineered 2022-03, Vol.13 (3), p.7648-7658
• Main Authors: Li, Jingrong, Fang, Ruihua, Wu, Jiang, Si, Yuan, Bai, Jingzhu, Wang, Qi
• Format: Article
• Language: English
• Subjects: beta Catenin - genetics; beta Catenin - metabolism; Cell Line, Tumor; Cell Proliferation; CSCs in melanoma; Endothelial Cells - metabolism; Gene Expression Regulation, Neoplastic; Humans; Melanoma - pathology; Neoplastic Stem Cells - metabolism; Neoplastic Stem Cells - pathology; NOP14; Nuclear Proteins - genetics; Research Paper; stemness; Wnt Signaling Pathway; wnt/beta-catenin signaling
• ISSN: 2165-5979; 2165-5987
• 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 in vitro. 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. Abbreviations: 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.