Circ_0003520/miR-205-5p/CUL4B Axis Drives the Progression of Clear Cell Renal Carcinoma

Abstract

Many circular RNAs (circRNAs) are frequently expressed in cancers and involved in cancer progression. Clear cell renal cell carcinoma (ccRCC) is a malignancy with a high mortality rate. A previous study has shown that circ_0003520 is increased in ccRCC. However. The action of circ_0003520 in ccRCC progression and its possible mechanisms remain unclear. Levels of circ_0003520, miR-205-5p and cullin 4B (CUL4B) were examined by qRT-PCR and western blot. Cell counting kit-8 (CCK-8), 5-ethynyl-2′ -deoxyuridine (EdU), flow cytometry, transwell, tube formation, and xenograft tumor assays were conducted to detect the effects of circ_0003520 on cRCC cell proliferation, apoptosis, migration, invasion, angiogenesis In Vitro, as well as tumor formation In Vivo. The binding between circ_0003520 or CUL4B and miR-205-5p was analyzed using dual-luciferase activity reporter assay and RNA immunoprecipitation (RIP) assay. We found that circ_0003520 and CUL4B expression was increased and miR-205-5p expression was decreased in ccRCC tissues compared to normal tissues. Circ_0003520 knockdown inhibited the proliferation, migration, invasion, and angiogenesis and promoted apoptosis in ccRCC cells in vitro, as well as inhibited tumor formation In Vivo. Further mechanism analysis showed that the miR-205-5p/CUL4B axis was the downstream target pathway of circ_0003520. Circ_0003520 could up-regulate CUL4B through sequestering miR-205-5p. Functionally, miR-205-5p inhibition or CUL4B overexpression could recover the inhibition mediated by circ_0003520 knockdown on ccRCC cell proliferation, migration, invasion, and angiogenesis, as well as the enhancement of cell apoptosis. Besides that, circ_0003520 also hindered tumor growth In Vivo via miR-205-5p/CUL4B axis. Circ_0003520 acts as an oncogene to promote ccRCC progression by regulating the miR-205-5p/CUL4B axis, indicating a promising strategy for suppressing ccRCC growth.