RNA-binding protein Epiplakin 1 promotes ovarian cancer immune escape and distal metastasis by enhancing the RNA stability of yes-associated protein.

This study investigated the mechanism of the RNA-binding protein Epiplakin 1 (EPPK1) in ovarian cancer (OC). EPPK1 expression in OC tissues was analyzed using gene expression profiling interactive analysis (GEPIA). The association between EPPK1 expression and patient overall survival (OS) and progression-free survival (PFS) was evaluated through Kaplan-Meier analysis. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blot were performed to quantify EPPK1 levels in 25 clinical OC specimens. An EPPK1-knockdown xenograft model was established to examine tumor growth and distant metastasis <i>in vivo</i>. The roles of EPPK1 and Yes-associated protein (YAP) in OC cell proliferation, migration, and immune escape were assessed <i>in vitro</i>. The EPPK1-YAP interaction was characterized. Analysis of the GEPIA database revealed elevated EPPK1 expression in ovarian serous cystadenocarcinoma, with Kaplan-Meier survival curves demonstrating significantly shorter OS and PFS in patients with high EPPK1 expression over a 5-year period. RT-qPCR and Western blot analyses confirmed EPPK1 upregulation in clinical OC specimens. Functional studies demonstrated that altered EPPK1 and YAP expression modulated OC cell proliferation, migration, invasion, and immune escape capabilities both <i>in vitro</i> and <i>in vivo</i>. Mechanistically, EPPK1 binds to and enhances YAP mRNA stability. Notably, YAP overexpression rescued the inhibitory effects of EPPK1 knockdown on OC cell proliferation, migration, invasion, and immune evasion <i>in vitro</i>. The results indicate that EPPK1 promotes immune evasion and distant metastasis in OC by stabilizing YAP RNA.