Abstract
Ovarian cancer (OC) is the predominant gynecological cancer and is associated with severe morbidity and high mortality worldwide. Therefore, clarifying the molecular mechanisms underlying OC progression and exploring novel therapeutic targets are important. Here, using human OC samples, different OC cell lines, and xenograft nude mouse models in combination with multiple sequencings, we report that hnRPD, an RNA binding protein that modulates RNA stability, is highly expressed in OC tissues, and contributes to OC cell malignancy in human OC cells cultured in vitro and in OC cell-derived xenograft nude mouse models in vivo. Mechanistically, ectopically expressed GPR137 binds to hnRPD and enhances hnRPD protein stability, which reciprocally transactivates GPR137 through the transcription factor FLI1. On the other hand, elevated hnRPD upregulates RAB8A expression by interacting with RAB8A mRNA and promoting its stability, leading to activation of downstream cell signaling and thereby enhanced OC cell malignant behaviors including cell proliferation, cell invasion, cell migration, and colony formation ability as well as OC xenograft growth in nude mice. Moreover, cisplatin in combination with silencing of hnRPD expression, significantly induces apoptosis in cisplatin-resistant OC cells through regulation of OC cell metabolism. Therefore, our data provide evidence that hnRPD could represent an innovative prognostic indicator for OC and may be an attractive therapeutic target for improving clinical outcomes in OC treatment.