1. Academic Validation
  2. SPOP attenuates migration and invasion of choriocarcinoma cells by promoting DHX9 degradation

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

  • Am J Cancer Res. 2020 Aug 1;10(8):2428-2445.
Dong Yuan 1 2 Yiyu Chen 2 Zhu Yang 1 2 Gang Li 2 Mingjun Wu 2 Jinyue Jiang 3 Dan Li 2 Qiubo Yu 2
Affiliations

Affiliations

  • 1 Department of Gynecology, The Second Affiliated Hospital of Chongqing Medical University Chongqing 400010, P. R. China.
  • 2 Molecular Medical Laboratory, Institute of Life Sciences, Chongqing Medical University Chongqing 400016, P. R. China.
  • 3 Department of Respiratory, The First Affiliated Hospital of Chongqing Medical University Chongqing 400016, P. R. China.
PMID: 32905556
Abstract

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.

Keywords

DHX9; EMT; SPOP; choriocarcinoma; ubiquitination.

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