circRNA DENND1B inhibits tumorigenicity of clear cell renal cell carcinoma via miR-122-5p/TIMP2 axis

Clear cell renal cell carcinoma (ccRCC) is the most common type of renal cancers. However, circ_DENND1B has not been studied yet. GSE100186 dataset was used for the level analysis of circ_DENND1B. The quantitative real-time PCR was used to verify the expression of circ_DENND1B, microRNA-122-5p (miR-122-5p) and tissue inhibitor of metalloproteinases-2 (TIMP2) in ccRCC tissues and cells. Cell proliferation, migration, invasion and apoptosis were detected by colony formation assay, thymidine analog 5-ethynyl-2′-deoxyuridine assay, 3-(4,5-dimethylthiazol-2-y1)-2,5-diphenyl tetrazolium bromide, transwell and flow cytometry. The binding of miR-122-5p to circ_DENND1B/TIMP2 was investigated by dual-luciferase reporter assay. Finally, the role of circ_DENND1B in ccRCC was detected by tumorigenesis experiment in mice. circ_DENND1B was downregulated in ccRCC and circ_DENND1B overexpression suppressed the malignant behaviors of ccRCC cells. circ_DENND1B acted as a sponge of miR-122-5p. miR-122-5p upregulation reversed the effects of circ_DENND1B on cell proliferation, migration, invasion and apoptosis. TIMP2 was a target of miR-122-5p. Overexpression of circ_DENND1B regulated TIMP2 level by inhibiting miR-122-5p expression in ccRCC cells. circ_DENND1B overexpression inhibited the tumor growth of ccRCC in vivo. circ_DENND1B inhibited ccRCC cell progression by promoting TIMP2 expression by sponging miR-122-5p, suggesting that circ_DENND1B might be an effective therapeutic target for ccRCC.