Circular RNAs (circRNAs) function as oncogenic factors or tumor repressors in variety of human malignancies. CircRNA Sodium Channel Epithelial 1 Subunit Alpha (circSCNN1A, hsa_circ_0025135) was downregulated in renal cell carcinoma (RCC). This study performed further research of circSCNN1A in RCC.The level detection for circSCNN1A, microRNA-421 (miR-421) or Membrane Palmitoylated Protein 7 (MPP7) was conducted by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Cell behaviors were analyzed by Cell counting kit-8 (CCK-8) assay for cell viability, EDU assay for cell proliferation, flow cytometry for cell apoptosis, transwell assay for cell invasion and tube formation assay for angiogenesis. The protein expression was determined using western blot. Dual-luciferase reporter assay, RNA immunoprecipitation (RIP) assay and pull-down assay were applied to validate the interaction between targets. In vivo research was performed by xenograft tumor assay.The level of circSCNN1A was significantly downregulated in RCC tissues and cells. RCC cell proliferation, invasion and angiogenesis were reduced but apoptosis was promoted by circSCNN1A overexpression. Interestingly, circSCNN1A could interact with miR-421. Overexpression of miR-421 has reversed the anti-tumor function of circSCNN1A in RCC cells. MPP7 served as a target of miR-421, and MPP7 inhibited the malignant phenotypes of RCC cells. In addition, miR-421 downregulation induced the inhibitory effect on the RCC development via elevating the MPP7 level. Moreover, RCC tumorigenesis was suppressed by circSCNN1A through the miR-421/MPP7 axis in vivo.The experimental data revealed that circSCNN1A upregulated the expression of MPP7 via sponging miR-421, then inhibiting the progression of RCC.Copyright © 2022 Elsevier B.V. All rights reserved.