Knockdown of Circ_0000798 Impedes Cell Growth and Motility of Renal Cell Carcinoma Cells Through Functioning as miRNA Sponge for miR-589-5p.

Abstract

GSE137836 and GSE100186 shows that upregulated hsa_circRNA_0000798 (circ_0000798) is associated with the development and progression of renal cell carcinoma (RCC). However, its biological functions in RCC cells remain unclarified. Here, we planned to explore its action and action of mechanism in RCC cells. Real-time quantitative PCR detected RNA expression and western blotting and immunohistochemistry measured protein expression. In vitro assays, including MTT, EdU, Transwell, and plate colony, scratch wound, apoptosis, and cell cycle assays, and in vivo xenograft tumor model were launched to measure cell dysfunctions. Dual-luciferase reporter assay and RNA pull-down were employed to identify target relationship. Circ_0000798 is upregulated in RCC patients' tumors and cells, and high circ_0000798 is associated with shorter overall survival. RNA interference of circ_0000798 impedes cell metabolic viability and abilities of DNA synthesis, colony formation, wound healing, migration, and invasion in RCC cells but also induces cell cycle arrest and apoptosis. Moreover, circ_0000798 interference could delay tumor growth in vivo. Proliferation markers Ki67 and Bcl-2 were depressed by inhibiting circ_0000798, accompanied with promoted levels of apoptosis proteins Bax and cleaved caspase-3. Of note, circ_0000798 functions as microRNA (miR) sponge for miR-589-5p and thus controls the expression of miR-589-5p-targeting Ras-GTPase-activating protein-binding protein 1 (G3BP1), a newly identified tumor-promoting gene in RCC. Their expressions are linearly correlated with each other in these tumor samples. Circ_0000798 might function oncogenic role in RCC and its downregulation could combat RCC cell growth and motility via targeting miR-589-5p/G3BP1 axis.