| Background:Esophageal cancer(EC)is one of the most aggressive cancers in the upper digestive system and is the sixth leading cause of cancer death worldwide.Esophageal cancer has put a serious threat to human health as well as a heavy burden on the social economy.Although esophageal cancer is a global disease,the incidence of esophageal cancer has obvious geographical distribution difference.China has a high incidence of esophageal cancer in the world,approximately 70% of global esophageal cancer cases occur in china,of which approximately 90% of cases are esophageal squamous cell carcinoma(ESCC).Despite the diagnosis and treatment of esophageal cancer are being optimized,the overall 5-year survival rate is only 15-25%.On the one hand,the symptoms of esophageal cancer in earlier stages is hidden,thus most of the patients were diagnosed in advanced stages and lost the chance of surgical resection.On the other hand,there is no highly efficient biomarker can diagnose early stage esophageal cancer or evaluate the recurrence,and no potential therapeutic target for esophageal cancer.Therefore,it is of great theoretical and practical significance to further explore the molecular mechanism of esophageal cancer.Long non-coding RNAs(lncRNAs)are non-protein coding transcripts with a length of 200-100000 nucleotides.Recent studies have shown that although long non-coding RNA does not encode proteins,it can participate in a variety of molecular and cellular processes,including: chromosome dosage-compensation,imprinting,cell cycle regulation,intracellular trafficking,epigenetic regulation,reprogramming and stem cell differentiation.Simultaneously,emerging evidences have showed that long non-coding RNA can regulate multiple developmental processes and human diseases.The most popular research at present is the relationship between long non-coding RNA and tumor,and some studies have shown that long non-coding RNA can be used as a specific biomarker and even a potential therapeutic target for certain cancers.About 98% of the genes in the human genome are transcribed into non-coding RNAs(ncRNAs),and the vast majority of them are long non-coding RNAs,these indicate that lncRNA is a vast untapped treasure trove for exploring the direction of tumor therapy.HOXA11-AS is a new type of long non-coding RNA located on chromosome 7p15.2.Some literatures have pointed out that HOXA11-AS plays an important role in ovarian cancer,gastric cancer and osteosarcoma,however,its study on esophageal squamous cell carcinoma has not been reported.Objective: The purpose of this study was to detect the expression of long non-coding RNA HOXA11-AS in human esophageal squamous cell carcinoma and three different human ESCC cell lines(Eca-109,KYSE-150 and KYSE-450),and to analyze the relationship between the expression level of lncRNA HOXA11-AS and the clinicopathological features of patients with esophageal squamous cell carcinoma,and to investigate the effects of lncRNA HOXA11-AS on the migration and proliferation of ESCC cell lines,and to find new efficient biomarkers and potential therapeutic targets for ESCC.Methods: 1.The specimens(tumor tissue and adjacent normal tissue)of this study come from 50 patients with esophageal squamous cell carcinoma who underwent surgical resection at Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital between May 2017 to November 2017.Quantitative real-time PCR(qRT-PCR)was performed to detect the expression level of lncRNA HOXA11-AS in the above specimens,and the relationship between the lncRNA HOXA11-AS expression level and the clinicopathological features of the patients with ESCC were analyzed.2.The same way was used to detect the HOXA11-AS expression in three kinds of human esophageal squamous cell carcinoma cell lines(Eca-109,KYSE-150 and KYSE-450).The highest expression one was selected for subsequent experiments.3.The HOXA11-AS was downgraded by small interfering RNA(siRNA)in the ESCC cell lines,and its effects on the proliferation and migration of esophageal cancer cells were detected by CCK-8(cell counting kit-8)assay and wound healing assay.Results: 1.The expression of long non-coding RNA HOXA11-AS in esophageal squamous cell carcinoma tissues are significantly higher than that in the adjacent normal esophagus tissues(P<0.01).2.The higher expression of long non-coding RNA HOXA11-AS in esophageal squamous cell carcinoma is related to tumor stage and lymph node metastasis(P<0.05),but it has nothing to do with age,sex,history of alcohol and tobacco,tumor position,tumor size,tumor gross form and the degree of tumor differentiation(P>0.05).3.Compared with the human normal esophageal epithelial cell lines,the long non-coding RNA HOXA1-AS was highly expressed in 3 kinds of human ESCC cell lines(P<0.05),and the expression level was highest in Eca109.4.After the specific siRNA interference,the expression level of the long non-coding RNA HOXA1-AS decreased significantly compared with the control group(P<0.05).The CCK-8 assay demonstrated that the proliferative ability of si-HOXA1-AS group was significantly decreased after transfection(P<0.05),and the inhibition of proliferation was more significant with the prolongation of time.The wound healing assay showed that the cell migration ability of si-HOXA11-AS group decreased significantly compared with the control group(P<0.05),and the difference was more obvious with the increase of time.Conclusion:1.The expression of long non-coding RNA HOXA1-AS in esophageal squamous cell carcinoma and human ESCC cell lines is significantly higher,and its high expression level is significantly correlated with tumor stage and lymph node metastasis,which indicates that HOXA1-AS may be used as a biomarker for the diagnosis and monitoring of ESCC.2.The down-regulation of long non-coding RNA HOXA11-AS in human ESCC cell lines can inhibit the proliferation and migration of cancer cells,indicating that HOXA11-AS may play a role as oncogene in the occurrence and development of ESCC,and may also be a potential therapeutic target for esophageal squamous cell carcinoma. |
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