Circular RNAs negatively regulate cancer stem cells by physically binding FMRP against CCAR1 complex in hepatocellular carcinoma.

摘要: Circular RNA (circRNA) possesses great pre-clinical diagnostic and therapeutic potentials in multiple cancers. It has been reported playing roles malignant behaviors including proliferation, migration, metastasis chemoresistance. However, the underlying correlation between circRNAs cancer stem cells (CSCs) not yet. Methods: circZKSCAN1 level was detected HCC tissue microarrays to clarify its prognostic values. Gain loss function experiments were applied investigate role of stemness. Bioinformatic analysis used predict possible downstream binding protein further immunoprecipitation sequencing carried out identify RBP-regulated genes. Results: The absence endowed several properties stemness tightly correlated with worse overall recurrence-free survival rate HCC. Bioinformatics immunoprecipitation-sequencing (RIP-seq) results revealed that exerted inhibitive by competitively FMRP, therefore, block FMRP β-catenin-binding protein-cell cycle apoptosis regulator 1 (CCAR1) mRNA, subsequently restrain transcriptional activity Wnt signaling. In addition, RNA-splicing Quaking 5 found downregulated tissues responsible for reduction circZKSCAN1. Conclusion: Collectively, this study mechanisms regulatory CSCs identified newly discovered Qki5-circZKSCAN1-FMRP-CCAR1-Wnt signaling axis as a potentially important target treatment.