RNF126 Promotes Ovarian Cancer Progression by Reprogramming Lipid Metabolism Through Degradation of ACAP2
Ovarian cancer (OC) primarily arises from heterogeneous malignant epithelial tissue in the ovary, fallopian tube, or peritoneum. Ubiquitin ligase Ring-finger protein 126 (RNF126) was aberrantly expressed in OC. However, its molecular mechanism is unknown. This study investigates the role and mechanism of RNF126 in regulating ArfGAP with coiled-coil, ankyrin repeat, and PH domains 2 (ACAP2) during OC progression. RT-qPCR and Western blot (WB) were used to assess the expression of RNF126, ACAP2, and lipid synthesis-related genes in OC tissues and cells. The proliferation and migration abilities of OC cells were detected by CCK-8 and Transwell assays. Nile red staining was used to detect the lipid accumulation. The interaction between RNF126 and ACAP2 in OC cells was detected using co-immunoprecipitation (Co-IP). The stability of the ACAP2 protein was analyzed using the cycloheximide (CHX) assay. The effect of RNF126 on tumor growth and metastasis in vivo was investigated by detecting tumor volume and size as well as the number of lung nodules. The expression of RNF126 was upregulated in OC tissues and cells, and RNF126 silencing significantly inhibited the proliferation, migration, and lipid accumulation of OC cells. Mechanistically, ACAP2 was identified as a ubiquitination substrate of RNF126, and its expression was negatively regulated by RNF126. Furthermore, RNF126 promoted OC progression both in vitro and in vivo by suppressing ACAP2 protein expression. RNF126 promotes ovarian cancer progression by reprogramming lipid metabolism via degrading ACAP2.