Circ_101341 Deteriorates the Progression of Clear Cell Renal Cell Carcinoma Through the miR- 411/EGLN3 Axis.

Abstract

BackgroundClear cell renal cell carcinoma (ccRCC) is one of the main subtypes of renal cell carcinoma, with intense aggressiveness. The involvement of circular RNAs (circRNAs) in human cancers attracts much concern. The intention of this study was to investigate the expression of circ_101341 and explore its function in ccRCC.Materials and MethodsThe expression of circ_101341, miR-411 and Egl nine homolog 3 (EGLN3) was measured using quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation was assessed by cell counting kit-8 (CCK-8) assay and colony formation assay. Cell migration and invasion were monitored by transwell assay. Xenograft model was established to explore the role of circ_101341 in vivo. The protein levels of E-cadherin (E-cad), N-cadherin (N-cad), matrix metalloprotein-9 (MMP9) and EGLN3 were detected by Western blot. Bioinformatic analysis was conducted using Circinteractome and starBase. The targeted relationship was verified using dual-luciferase reporter assay, RNA-binding protein immunoprecipitation (RIP) assay and RNA pull-down assay.ResultsThe expression of circ_101341 was elevated in ccRCC tissues and cells. Functionally, circ_101341 knockdown depleted proliferation, migration and invasion of ccRCC cells in vitro and restricted tumor growth in vivo. Circ_101341 directly targeted miR-411, and miR-411 inhibition revised the inhibitory effects of circ_101341 knockdown on proliferation, migration and invasion in ccRCC cells. Moreover, miR-411 directly bound to EGLN3, and EGLN3 overexpression also rescued the effects of circ_101341 knockdown.ConclusionCirc_101341 functioned as a tumor promoter to strengthen proliferation, migration and invasion by regulating EGLN3 via sponging miR-411, indicating that circ_101341 was a potential diagnostic and therapeutic biomarker of ccRCC.