RESUMO
Studies on clear cell renal cell carcinoma (ccRCC) are gaining momentum due to its high malignancy and potential to metastasize. Fbox protein 30 (FBXO30) is a member of the Fbox protein family; however, its role and mechanism in cancer remains to be fully elucidated. Western blotting, reverse transcriptionquantitative PCR and immunohistochemsitry were performed to detect the expression levels of FBXO30 in ccRCC tissues and adjacent normal tissues. Tumor biological function assays and animal experiments were conducted to clarify the inhibitory effect of FBXO30 on the progression and metastasis of ccRCC. Protein halflife assay, MG132 inhibition assay, immunofluorescence assay and coimmunoprecipitation assay were performed to explore the ubiquitination mechanism of FBXO30 and HIF1α. Zinc supplementation assay was used to verify the regulatory relationship between human ZRT, IRTlike protein 1 (hZIP1), FBXO30 and HIF1α. The present study revealed that the expression levels of FBXO30 were lower in ccRCC tissues compared with those in normal adjacent tissues. In addition, FBXO30 inhibited the tumorigenesis and metastatic capacity of ccRCC cells in vivo and in vitro. FBXO30 mediated the ubiquitination and degradation of hypoxiainducible factor1α (HIF1α) in ccRCC cells under normoxia, thereby inhibiting the oncogenic effect of HIF1α. Notably, hZIP1 served as an upstream regulator of FBXO30, regulating the expression of FBXO30 and HIF1α by recruiting Zn2+. In conclusion, the present data suggested that FBXO30 is a novel E3 ubiquitination ligase that can function as a tumor suppressor in ccRCC, and the hZIP1/Zn2+/FBXO30/HIF1α axis may provide potential biomarkers or therapeutic targets for ccRCC.