Overexpression of RNF180 Inhibits Progression and Metastasis by Epithelial Mesenchymal Transformation and Immune Infiltration in Renal Cancer

Abstract

Background: Molecular biomarkers combined with histopathological examination are of critical importance in the diagnosis and treatment of clear cell renal cell carcinoma (ccRCC). The occurrence and development of ccRCC is closely related to abnormal E3 ubiquitin enzyme. Although recent studies have revealed that Ring Finger Protein 180 (RNF180)，known as an E3 ubiquitination enzyme, could regulate the cell proliferation, and differentiation in different cancers, the precise role of RNF180 in renal cancer remains to be elucidated. Methods: Western-blot, qPCR and CCK-8 assay were performed to initially explore and further validate the function of RNF180. The effect of RNF180 on cell migration and invasion was verified by Transwell assay and EdU assay. The morphology of the tissue slides was evaluated by HE staining and immunohistochemical assay. Cell line-derived xenograft models in mice further validated the effect of RNF180 in vivo. Bioinformatics tools based on public databases were used to assess patient survival and immune infiltration.Results: RNF180 is significantly down-regulated in multiple cancer-related databases and ccRCC cell lines. By using immunohistochemical analysis, we found that the expression level of RNF180 was also downregulated in ccRCC and the lower expression level of the RNF180 was associated with poorer clinical outcomes in renal cancer patients. Overexpression of RNF180 inhibits proliferation, migration and invasion of ccRCCs in vitro. In vivo, RNF180 could also modulate renal cancer progression in murine subcutaneous xenografts and liver metastasis. Strikingly, we further investigated the underlying mechanism and found that overexpression of RNF180 inhibited the progression of ccRCC by reducing epithelial-mesenchymal transformation (EMT) and may related to immune infiltration.Conclusion: These results indicated that RNF180 can be used as a new diagnostic marker and prognostic factor, and can be served as a therapeutic target for ccRCC.