Exosome-transmitted LncRNA UFC1 Promotes Non-small-cell Lung Cancer Progression Via Regulating Epigenetic Silencing Of PTEN Expression

Background: Non-small cell lung cancer(NSCLC)has high morbidity and mortality and poor prognosis.Long non-coding RNAs(lnc RNAs)have been suggested as important regulators of cancer development and progression in non-small cell lung cancer(NSCLC).Nevertheless,the biological roles and clinical significance of lnc RNA UFC1 in NSCLC remain unclear.Methods:In this study,the expression of lnc RNA UFC1 was detected in tumor tissues,serum and serum exosomes of NSCLC patients by q RT-PCR.The association with clinicopathological parameters was analyzed.Cell counting,colony formation,transwell migration and matrigel invasion assays,and flow cytometry analyses were used to exa分钟e NSCLC cell proliferation,migration,invasion and apoptosis.RNA immunoprecipitation assay was performed to evaluate the interaction between lnc RNA UFC1and enhancer of zeste homolog 2(EZH2).Ch IP assay was used to deter分钟e the binding of EZH2 to PTEN gene promoter.Mouse xenograft tumor model was performed to evaluate the effect of lnc RNA UFC1 on NSCLC growth.Rescue study was used to access the importance of PTEN regulation by lnc RNA UFC1 in NSCLC progression.Results: lnc RNA UFC1 expression was up-regulated in tumor tissues,serum,and serum exosomes of NSCLC patients and a higher level of lnc RNA UFC1 was associated with increased tumor infiltration.lnc RNA UFC1 knockdown inhibited NSCLC cell proliferation,migration and invasion while promoted cell cycle arrest and apoptosis.Overexpression of lnc RNA UFC1 led to the opposite effects.Mechanistically,lnc RNA UFC1 bound to EZH2 and mediated its accumulation at the promoter region of PTEN gene,leading to the trimethylation of H27K3 and the inhibition of PTEN expression.lnc RNA UFC1 knockdown also inhibited NSCLC growth in mouse xenograft tumor models while the simultaneous depletion of PTEN reversed this role.Moreover,NSCLC cells derived exosomes could promote NSCLC cell proliferation,migration,and invasion through the delivery of lnc RNA UFC1.Conclusions: Exosome-transmitted lnc RNA UFC1 promotes NSCL C progression by inhibiting PTEN expression via EZH2-mediated epigenetic silencing.Exosomal lnc RNA UFC1 may serve as a novel biomarker for NSCLC diagnosis,prognosis and therapy.