SPOP attenuates migration and invasion of choriocarcinoma cells by promoting DHX9 degradation

Speckle-type POZ protein (SPOP), a novel cancer- associated protein, was previously reported to function as a tumor suppressor or promoter in different malignant tumors. This research aims to investigate the biological functions and underlying molecular mechanisms of SPOP in choriocarcinoma. Our analysis of patient tissues and cell lines showed significantly decreased SPOP expression and highly expressed Nuclear DNA helicase II and RNA helicase A (DHX9), both of them are mainly located into the nucleus. Induction or depletion of endogenous SPOP with a lentivirus-based system correspondingly suppressed or promoted migration and invasion of choriocarcinoma cells. Mechanistically, we found that SPOP bound to DHX9 and induced the ubiquitination and degradation of DHX9 by recognizing a typical SPOP-binding motif in DHX9. SPOP-DHX9 interaction was demonstrated to play a critical role in regulating migration and invasion abilities of choriocarcinoma cells, the promotion of mobility ability in knocking down SPOP was partly counteracted by transfection with siRNA against DHX9. Taken together, our results suggest that SPOP suppresses migration and invasion of choriocarcinoma by promoting the ubiquitination and subsequent degradation of DHX9, which identifies the SPOP-DHX9 interaction may serve as a potential therapeutic target against choriocarcinoma.