Long Noncoding RNA CCDST Regulates Cervical Cancer Motility And Angiogensis By Degrading DHX9 Via Recuiting The E3 Ligase MDM2

Background:Cervical cancer is the third most common female carcinoma worldwide and the fourth leading cause of cancer-associated mortality in women.Cervical cancer may be completely free of symptoms in the early stages but may be present in the abdomen,lungs,or elsewhere.The molecular mechanisms underlying the progression of cervical cancer remain unclear.Methods:Long non-coding RNA(lncRNA)microarray were used to identify the lncRNA expression profiles in cervical cancer tissues.Overexpression and knockdown of genes were achieved with lentiviral vectors or siRNAs.RNA-protein pulldown and mass spectrometry were performed to investigate lncRNA binding proteins.All statistical tests were two-sided.Results:MDM2-DHX9 interaction mediates cervical cancer motility and angiogenesis in a lnc-RHA-dependent fashion.lnc-CCDST,which binds to DHX9,is significantly down-regulated in cervical cancer tissues.DHX9 is up-regulated in cervical cancer tissue,and promotes cervical cancer cell motility and angiogenesis.The lnc-CCDST and DHX9 interaction promotes DHX9 degradation through ubiquitin proteasome pathway.Furthermore,DHX9 bound to E3 ubiquitin ligase MDM2,and this interaction is enhanced by lnc-CCDST.Moreover,HPV oncogenes E6 and E7 abolish the expression of lnc-CCDST resulting in the increase of DHX9.Conclusions:High risk HPVs promote motility and angiogenesis of cervical cancer by inhibiting the expression of lnc-CCDST to disrupt MDM2 and DHX9 interaction,and DHX9 degradation,and identified a potential therapeutic target for cervical cancer.