Ring Finger Protein 217 Inhibits Ovarian Cancer Progression by Down-Regulating HAX1 Expression

Ring finger protein 217 (RNF217) has been found to interact with the antiapoptotic protein HS-1-associated protein X-1 (HAX-1) in myeloid leukemia cells. However, the understanding of RNF217 in ovarian cancer progression remains limited. The relative expression of RNF217 is screened in ovarian cancer using the GEPIA database and calculated its correlation with MKI67, CCNB1, and CDK4. OVCAR-3 and SK-OV-3 cells are transfected with RNF217-overexpression plasmids. Cell-counting kit-8 assay is utilized to assess proliferation. Immunoprecipitation is performed to reveal the interaction between RNF217 and HAX-1, and a cycloheximide chase assay is performed to analyze HAX-1 degradation. The GEPIA database indicated down-regulated expression of RNF217 in ovarian cancer, negatively correlated with MKI67 (R = -0.26, P = 1.8e-09), CCNB1 (R = -0.37, P = 3.2e-18), and CDK4 expression (R = -0.24, P = 3.4e-08). RNF217 overexpression down-regulated the relative expression of MKI67, CCNB1, and CDK4 in OVCAR-3 and SK-OV-3 cells, resulting in diminished proliferation. In vivo studies using OVCAR-3 and SK-OV-3 cell line-derived xenograft models also showed that RNF217 overexpression reduced ovarian cancer volume and weight. Furthermore, RNF217 overexpression in SK-OV-3 cells inhibited the protein expression of HAX1 by reducing its stability. In conclusion, RNF217 inhibits ovarian cancer progression by down-regulating HS-1-associated protein X-1 expression.