RESUMEN
BACKGROUND: Circular RNAs (circRNAs) have been reported to have critical regulatory roles in tumor biology. However, their contribution to melanoma remains largely unknown. METHODS: CircRNAs derived from oncogene CD151 were detected and verified by analyzing a large number of melanoma samples through quantitative real-time polymerase chain reaction (qRT-PCR). Melanoma cells were stably transfected with lentiviruses using circ_0020710 interference or overexpression plasmid, and then CCK-8, colony formation, wound healing, transwell invasion assays, and mouse xenograft models were employed to assess the potential role of circ_0020710. RNA immunoprecipitation, luciferase reporter assay and fluorescence in situ hybridization were used to evaluate the underlying mechanism of circ_0020710. RESULTS: Our findings indicated that circ_0020710 was generally overexpressed in melanoma tissues, and high level of circ_0020710 was positively correlated with malignant phenotype and poor prognosis of melanoma patients. Elevated circ_0020710 promoted melanoma cell proliferation, migration and invasion in vitro as well as tumor growth in vivo. Mechanistically, we found that high level of circ_0020710 could upregulate the CXCL12 expression via sponging miR-370-3p. CXCL12 downregulation could reverse the malignant behavior of melanoma cells conferred by circ_0020710 over expression. Moreover, we also found that elevated circ_0020710 was correlated with cytotoxic lymphocyte exhaustion, and a combination of AMD3100 (the CXCL12/CXCR4 axis inhibitor) and anti-PD-1 significantly attenuated tumor growth. CONCLUSIONS: Elevated circ_0020710 drives tumor progression via the miR-370-3p/CXCL12 axis, and circ_0020710 is a potential target for melanoma treatment.
Asunto(s)
Biomarcadores de Tumor/metabolismo , Quimiocina CXCL12/metabolismo , Regulación Neoplásica de la Expresión Génica , Melanoma/patología , MicroARNs/genética , ARN Circular/genética , Tetraspanina 24/genética , Animales , Apoptosis , Biomarcadores de Tumor/genética , Estudios de Casos y Controles , Movimiento Celular , Proliferación Celular , Quimiocina CXCL12/genética , Progresión de la Enfermedad , Femenino , Humanos , Evasión Inmune , Masculino , Melanoma/genética , Melanoma/inmunología , Melanoma/metabolismo , Ratones , Ratones Endogámicos C57BL , Persona de Mediana Edad , Invasividad Neoplásica , Pronóstico , Tasa de Supervivencia , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
BACKGROUND: Nuclear auto-antigenic sperm protein (NASP) has been implicated in tumorigenesis. However, its role in melanoma is still unclear. MATERIALS AND METHODS: In the present study, we detected the mRNA and protein level of NASP in melanoma cell lines and tissues. Then the role of NASP was investigated by transfecting with NASP siRNAs. Finally, the prognosis of NASP was analyzed in 100 melanoma patients through Cox regression and Kaplan-Meier analyses. RESULTS: We showed that NASP was significantly overexpressed in melanoma tissues, and unregulated NASP promoted melanoma cell proliferation via promoting cell cycle G1/S phase transition. Additionally, the expression of NASP was closely related to proliferating cell nuclear antigen, a widely accepted biomarker for cell proliferation. Clinically, we found that a high level of NASP predicated poor overall survival and high cumulative recurrence rates. Multivariate analysis revealed that NASP was a risk biomarker for predicting the prognosis of melanoma patients. CONCLUSION: Elevated NASP plays an important role in melanoma cell proliferation and tumor progression, and it can be used as an independent prognostic biomarker for melanoma patients.
