Whole Genome Analysis Of Long Non-coding RNA And Its Expression In Esophageal Cancer And Its Carcinogenic Effects

Background: Esophageal cancer is one of the most common cancers,and a leading cause of cancer-related death worldwide.However,the mechanism of esophageal cancer pathogenesis remains poorly understood.Long noncoding RNAs(lnc RNAs)dysregulation have been reported to involve in various human cancers,which highlights the potential of lnc RNAs used as novel biomarkers for cancer diagnosis.Although lots of efforts have been made to identify novel lnc RNAs signature in esophageal cancer,the expression pattern,prognostic value,and biological function of most lnc RNAs in esophageal cancer still need to be systematically investigated.Objective: In this study,we aimed to analyze the lnc RNAs’ profiling in human esophageal cancer tissues compared with normal tissues,thereby identifying more esophageal cancer associated lnc RNAs.In addition,we validated one of these lnc RNAs function and potential underlying involved pathways in esophageal cancer.Our findings may provide new targets for the diagnosis and treatment of esophageal cancer.Methods: In this study,we comprehensively analyzed the expression profile of lnc RNAs in more than 200 esophageal cancer patients tissue samples from The Cancer Genome Atlas(TCGA)and Gene Expression Omnibus(GEO).We used the univariate Cox proportional hazard regression model(Cox Proportion-Hazards model)to analyze the relationship between lnc RNA expression levels and overall Survival and Recurrence Free Survival in patients with esophageal cancer.In addition,we applied quantitative PCR to detect the expression level of lnc RNA DXUAP8 in esophageal cancer tissues and normal tissues,and analyzed its correlation with pathological features of patients with esophageal cancer.Finally,we used si RNA to knock down the expression level of DUXAP8 in esophageal cancer cells,CCK8,colony formation,flow cytometry and transwell assays to detect the effect of knockdown of DUXAP8 on proliferation and invasion of esophageal cancer cells.Results: We identified thousands of lnc RNAs are differentially expressed in esophageal cancer tissues,and many of those lnc RNAs expression are associated with patients overall survival or recurrence free survival time.Moreover,copy number variation analyses revealed that genomic loci copy number amplification or deletion might contribute to these lnc RNAs dysregulation.Among these lnc RNAs,DUXAP8 and LINC00460 were significantly up-regulated,and GO enrichment analyses indicated that the two lnc RNAs associated protein coding genes involve with many known biological processes,such as cell cycle,and cell-cell adherens junction.Further experimental validation revealed that knockdown of DUXAP8 could impair esophageal cancer cells proliferation and invasion in vitro.Conclusion: Taken together,our findings identified lots of aberrantly expressed lnc RNAs in esophageal cancer that may provide a useful resource for identifying novel esophageal cancer associated lnc RNAs.Highly expressed DUXAP8 participates in the occurrence and development of esophageal cancer by affecting the proliferation and invasion of esophageal cancer cells.