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The article describes a study on renal cell carcinoma (RCC) metastasis and the involvement of circular RNAs (circRNAs) in this process. The researchers identified a highly metastatic clone in recurring lung-metastasis cases using patient-derived xenograft models and found that circSPIRE1 is a metastasis-inhibiting circRNA in clinical cohort and xenograft models. The mechanism involves circSPIRE1 suppressing mesenchymal state through regulating ELAV like RNA binding protein 1-mRNA binding, and upregulating polypeptide N-acetylgalactosaminyltransferase 3 (GALNT3) and KH domain RNA binding protein (QKI) expression. GALNT3 promotes glycosylation and cytomembrane localization of E-cadherin, while QKI forms a positive feedback loop to enhance circSPIRE1 expression. Exosomal circSPIRE1 suppresses angiogenesis and vessel permeability. Finally, the researchers suggest that circSPIRE1 may be a predictor of metastasis and a potential therapeutic target of metastatic RCC.
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