| Background and objective: China is one of the countries with a high incidence of esophageal cancer(EC)and the incidence of esophageal cancer patients in China accounts for 46.6% of the world's.In China,esophageal squamous cell carcinoma(ESCC)accounts for more than 90% of EC,which seriously threatens the health and life safety of Chinese people.There are no obvious clinical signs and symptoms in the early stage of ESCC,many patients are diagnosed in the middle or late stage with lymph node metastasis.Due to the lack of reliable therapeutic targets for this disease,the prognosis is poor and the overall 5-year survival rate is low.Therefore,in-depth study of the underlying molecular mechanisms in the progression of esophageal cancer is of great significance for its targeted treatment and prognosis improvement.Long non-coding RNA(lncRNA)is an important new member of the non-coding RNA(ncRNA)family,transcripts >200 nucleotides in length and with no protein coding potential.LncRNA plays an important role in chromatin modification,transcription,translation,splicing,epigenetic regulation and other biological processes.Currently,it has been confirmed that lncRNA is abnormally expressed in breast cancer,gastric cancer,liver cancer,esophageal cancer and other tumors,and itplays an important role in the proliferation,apoptosis,infiltration and epithelial interstitial transformation of tumor cells,and can be used as a potential marker for tumor therapy and prognosis.FEZ family zinc finger 1 antisense RNA 1(FEZF1-AS1),an lncRNA with a length of 2564 bp,which located in chromosome 7.Studies have confirmed that FEZF1-AS1 is overexpressed in gastric cancer,and knockout of FEZF1-AS1 can significantly inhibit the proliferation of gastric cancer cells in vitro and in vivo,and inhibit cell cycle progression by causing G1/S arrest.In addition,FEZF1-AS1 is also significantly up-regulated in non-small cell lung cancer(NSCLC)tissues,and the increased expression level of it is related to the lymph node metastasis,differentiation degree and TNM stage of NSCLC patients,and down-regulated FEZF1-AS1 expression could inhibits the proliferation and invasion ability of NSCLC cells.These studies indicate that FEZF1-AS1 plays an important role of oncogenes in some tumors.However,the role and mechanism of FEZF1-AS1 in ESCC remain unclear,which needs to be further clarified.In this study,we detected the expression level of FEZF1-AS1 in 45 cases of ESCC tissues and adjacent non-tumorous tissues and analyzed the relationship between FEZF1-AS1 expression and the clinical characteristics of patients with ESCC.By knockdown or over-express the level of FEZF1-AS1 in ESCC cells,we tested the influence of FEZF1-AS1 on the biological behaviors of esophageal squamous cell carcinoma cells,such as cell proliferation,cell cycle,cell migration and invasion.In addition,we preliminarily discussed the molecular mechanism of FEZF1-AS1 in ESCC,so as to provide a new experimental basis for FEZF1-AS1 to become a potential clinical therapeutic target of ESCC.Methods: 1 Quantitative real-time polymerase chain reaction(qRT-PCR)was used to detect the expression level of FEZF1-AS1 in ESCC tissues and cell lines.Statistical software was used to analyze the correlation between FEZF1-AS1 expression and clinicopathological factors of ESCC patients.2 The siRNAs was used to knockdown the expression of FEZF1-AS1 in EC9706 and EC1 cell lines,and GV219-FEZF1-AS1 plasmid was used to up-regulate theexpression of FEZF1-AS1 in the contrary.WST-1 assays,cell cycle assays and transwell assays were used to investigate the influence of FEZF1-AS1 knockdown and overexpression on the biological function of ESCC cells.3 The possible downstream target genes of FEZF1-AS1 were analyzed,and the mRNA expression levels of it in ESCC tissues,pre-transfection and post-transfection ESCC cell lines were detected by RT-qPCR,so as to explore the molecular mechanism of FEZF1-AS1 in esophageal squamous cell carcinoma.Results: 1 The expression level of FEZF1-AS1 was significantly higher in ESCC tissues than that in adjacent non-tumorous tissues,and its high expression was correlated with lymph node metastasis status of patients(P<0.05).2 The level of FEZF1-AS1 in EC9706 and EC1 cell lines was significantly higher than that in normal esophageal epithelial cell line Het-1A(P<0.05).Knockdown of FEZF1-AS1 in ESCC cells could significantly inhibited its migration and invasion(P<0.05).Overexpression of FEZF1-AS1 could significantly promoted the migration and invasion of ESCC cells(P<0.05).3 ?-catenin was up-regulated in ESCC tissues(P<0.05)and positively correlated with the expression level of FEZF1-AS1 in tissues(r=0.656).After knockdown or overexpression of FEZF1-AS1 in esophageal cancer cell lines EC1 and EC9706,the expression of ?-catenin was subsequently decreased or up-regulated(P<0.05).Conclusion: The results of this study showed that FEZF1-AS1 was obviously up-regulated in ESCC tissues.The expression of FEZF1-AS1 in tissues displayed a significant positive correlated with the expression of ?-catenin and its high expression was correlated with patient's lymph node metastasis.Knockdown or overexpress FEZF1-AS1 could significantly inhibited or promoted the migration and invasion of ESCC cells.This process might be achieved through the Wnt/?-catenin pathway. |
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