Abstract
Zinc figure CCCH-type containing 15 (ZC3H15), also called developmentally regulated GTP-binding protein 1 (DRG1) family regulatory protein 1 (DFRP1), is a zinc finger containing protein. Despite playing a role in cellular signaling, it is found overexpressed in acute myeloid leukemia and also an independent prognostic marker in hepatocellular carcinoma patients. However, the biological effect of ZC3H15 in malignant melanoma (MM) remains unexplored. The expression of ZC3H15 in patients was analyzed using the R2: Genomics Analysis and Visualization Platform database. Immunohistochemical analysis, western blot, and qRT-PCR were used to detect ZC3H15 expression in melanoma tissues and cell lines. MTT, BrdU, flow cytometry assay, transwell, and western blot were performed to explore the proliferation, cell cycle, invasion, and migration of melanoma cells. We undertaken colony formation assay in vitro and tumor xenograft in vivo to detect the tumorigenicity of melanoma cells. In the present study, ZC3H15 was demonstrated highly expressed in melanoma tissues and cells. Elevated ZC3H15 impairs the survival of melanoma patients. Meanwhile, attenuation of ZC3H15 in melanoma cells inhibited cell proliferation and induced cycle arrest at G0/G1 phase. Consistently, the expression of cell cycle-related proteins cyclin dependent kinase 4 (CDK4), CDK6, and cyclin D1 (CCND1) was decreased while p21 was upregulated. Furthermore, we found the migration and invasion abilities were inhibited in ZC3H15-knockdown melanoma cells. In addition, downregulation of ZC3H15 resulted in inhibition of colony formation abilities in vitro and tumorigenesis in vivo. ZC3H15 promotes proliferation, migration/invasion, and tumorigenicity of melanoma cells. As a promising biomarker and therapeutic target in MM, ZC3H15 is worthy of further exploration.
Highlights
Malignant melanoma (MM), a malignant transformation of melanocytes located within the deep layer of the epidermis [1], accounts for the fifth most common form of cancer in adults [2]
The long-term survival outcomes of metastatic melanoma have been dramatically improved by the development of immune checkpoint blockade strategies targeting the PD-1 and CTLA-4 coinhibitory receptors and MAPK molecular targeted therapy directed at oncogenic BRAF and MEK signaling pathways [2, 8]
To explore whether ZC3H15 could be a prognosis marker for melanoma, IHC was performed to detect the expression of ZC3H15
Summary
Malignant melanoma (MM), a malignant transformation of melanocytes located within the deep layer of the epidermis [1], accounts for the fifth most common form of cancer in adults [2]. It can implicate multiple organs, including the eye, gastrointestinal tract, genitalia, sinuses, and meninges, but most commonly arises in the skin, especially in the setting of UV injury [2]. The long-term survival outcomes of metastatic melanoma have been dramatically improved by the development of immune checkpoint blockade strategies targeting the PD-1 and CTLA-4 coinhibitory receptors and MAPK molecular targeted therapy directed at oncogenic BRAF and MEK signaling pathways [2, 8]. There is an urgent need to explore new therapeutic target for MM
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