Abstract
BackgroundCircular RNAs (circRNAs) have been reported to have critical regulatory roles in tumor biology. However, their contribution to melanoma remains largely unknown.MethodsCircRNAs 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.ResultsOur 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.ConclusionsElevated circ_0020710 drives tumor progression via the miR-370-3p/CXCL12 axis, and circ_0020710 is a potential target for melanoma treatment.
Highlights
Circular RNAs have been reported to have critical regulatory roles in tumor biology
We identified a novel circRNA derived from the CD151, termed circ_0020710, was significantly overexpressed in melanoma tissues compared with matched normal tissues and benign nevi tissues, and high circ_0020710 level was positively correlated with poor prognosis of melanoma patients
Analysis of CD151-derived circRNAs in melanoma Previous studies have shown that CD151 is overexpressed in multiple tumors and participates in tumor progression [9, 11,12,13]
Summary
Circular RNAs (circRNAs) have been reported to have critical regulatory roles in tumor biology. Their contribution to melanoma remains largely unknown. The prognosis of melanoma patients has improved largely. Unlike linear RNA terminating with a 5’cap and a 3′ poly (A) tail, circRNAs have a covalently closed-loop structure [3]. Due to this property, circRNAs have strong resistance to exonucleolytic degradation and maintain high cellular stability [4, 5]. Few studies have linked circRNAs to the biological behavior of melanoma, which is of great significance
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