circKL inhibits the growth and metastasis of kidney cancer by sponging miR‑182‑5p and upregulating FBXW7

Abstract

Circular RNAs (circRNAs) are a type of non-coding RNA with important roles in the regulation of various biological processes involved in malignant progression. However, the potential molecular mechanisms and roles of circRNAs in kidney cancer have remained to be fully elucidated. In a previous study by our group, high-throughput microarray sequencing data were analyzed to determine the differentially expressed circRNAs in kidney cancer. In this analysis, a novel circRNA (hsa_circ_0100312, named circKL) was identified as a frequently downregulated circRNA in kidney cancer cells and tissues by reverse transcription-quantitative PCR. In the present study, Cell Counting Kit-8, colony formation, Transwell, wound-healing and mouse xenograft assays as well as a lung metastasis experiment were performed to confirm the functions of circKL. The experiments confirmed that circKL overexpression significantly inhibited the proliferation, migration, tumor growth and metastasis of kidney cancer both in vitro and in vivo. The potential molecular mechanisms of circKL were investigated by performing dual-luciferase and RNA immunoprecipitation assays. Western blot assays confirmed that overexpression of circKL significantly increased the protein level of F-box and WD repeat domain containing 7 (FBXW7). All results suggested that circKL suppressed the growth and migration of kidney cancer by sponging microRNA (miR)-182-5p and upregulating FBXW7 expression. Overall, the circKL/miR-182-5p/FBXW7 axis was indicated to have a key role in the growth and metastasis of kidney cancer and may be targeted as a novel therapeutic strategy.

FBXW7 attenuates tumor drug resistance and enhances the efficacy of immunotherapy

“…The similar phenonenon can also be found in other cancers. In CC cells and renal cancer cells, miR-182-5p directly binds to the 3’-UTR of FBXW7 mRNA and inhibits the expression of wild-type FBXW7 proteins because FBXW7 contains a hypothesized binding site for miR-182-5p in its 3’-UTR ( 79 , 80 ).…”