| Background and objective:Esophageal cancer(EC)is one of the most serious cancers,leading to cancer-related death all over the world.Recently,although the treatment level of esophageal cancer has been improved to some extent,while the prognosis of esophageal cancer patients is still poor,and the five-year survival rate is low.Studies have shown that the pathogenesis of esophageal cancer is the common result of the abnormal multi gene,multi-step and multi signal transduction pathway.Therefore,it has become a research hotspot to explore the molecular mechanism of the occurrence and development of esophageal cancer and find new therapeutic markers on this basis.Previous studies have reported that the molecular mechanism and coding genes of the occurrence and development of esophageal cancer are closely related to the activation of proto-oncogenes and the inactivation of tumor suppressor genes.With the development of sequencing technology,noncoding RNA has become a research hotspot.Long non-coding RNA(lncRNA)are a subgroup of RNA molecules which are longer than 200 nucleotides without protein-coding ability,but plays an important regulatory role in the human genome.Accumulating evidence reveals that lncRNAs are often dysregulated expression leading to carcinoma's progression and metastasis through diverse mechanisms,such as epigenetic modifications,transcriptional interference and transcriptional activation.Emerging studies have found that abnormal expression of lncRNAs are closely related to the occurrence and development of multiple cancers,and may serve as tumor suppressors or oncogenes.Therefore,we can find tumor specific lncRNAs,reveal its potential mechanism in tumor development,and find its potential diagnosis and treatment targets.LncRNA MNX1-AS1(Motor neuron and pancreas homeobox 1-antisense RNA1)with a 992bp,located on chromosome 7.Recent studies have confirmed that MNX1-AS1 is significantly up-regulated in colon cancer tissues,which promotes the progression of colon cancer by regulating miR-218-5p/SEC61Alaxis.In addition,MNX1-AS1 was also found to be up-regulated in breast cancer,which induced the epithelial mesenchymal transition by activating the AKT/mTOR pathway.These studies show that MNX1-AS1 can play the role of oncogenes in tumor progression.However,the role and mechanism of MNX1-AS1 in esophageal cancer are still unclear,which needs further study.In this study,to further estimate the clinicopathological features of MNX1-AS1 level in ESCC patients was analyzed by detecting the expression level of MNX1-AS1 in 45 ESCC patients and adjacent non-tumorous tissues.The effects of MNX1-AS1 on the proliferation,cell cycle,apoptosis,migration and invasion of ESCC cells were studied by constructing the MNX1-AS1 knockdown ESCC cell model.In addition,the molecular mechanism of MNX1-AS1 in ESCC was discussed,which provided theoretical basis for the occurrence and development of ESCC.Methods:1 The expression levels of 45 pairs of ESCC and corresponding tumor-adjacent tissues were detected by qRT-PCR,and clinicopathological features of MNX1-AS1 level in ESCC patients was analyzed.2 Using siRNA to knock down the expression of MNX1-AS1 in KYSE30 and KYSE150 cells,through WST-1 proliferation,cell cycle,apoptosis and transwell migration and invasion experiment,to explore the the biological effects of knockdown MNX1-AS1 in ESCC cells.3 Using bioinformatics software to predict miR-34a was the target gene of MNX1-AS1,qRT-qPCR was performed to detect the mRNA expression level in ESCC tissue and ESCC cell line after siRNA transfection,and the effects of miR-34a and MNX1-AS1 on the biological function of ESCC cell were analyzed.4 SIRT1 may be the target gene of miR-34a.qRT-PCR was determined to detect the mRNA expression level in ESCC cell lines after knockdown of miR-34a and MNX1-AS1,and to explore the molecular mechanism of MNX1-AS1 in ESCC.Results:1 The expression level of MNX1-AS1 in ESCC was higher than that in the matched adjacent tissues.In addition,the expression level of MNX1-AS1 was related to the lymph node metastasis of ESCC patients(P<0.05).2 After knockdown MNX1-AS1 the capacity of ESCC proliferation,migration and invasion were decreased(P<0.05).MNX1-AS1 could regulate ESCC cell cycle and apoptosis.The flow cytometry assay indicated that inhibiting MNX1-AS1 expression in KYSE30 cells increased the percentage of cells in the G1 phase and decreased the percentage of cells in the S phase.3 The expression of miR-34a in ESCC was downregulated,and the expression of miR-34a was negatively correlated with the expression of MNX1-AS1.The expression level of miR-34a increased significantly after targeted knockdown MNXI-AS1.Migration experiments showed that inhibiting miR-34a expression could partially reverse the migration ability of MNX1-AS1 in ESCC cells.4 SIRT1 expression was up-regulated in ESCC.After knockdown MNX1-AS1,the expression level of SIRT1 was decreased.After knockdown miR-34a,the expression level of SIRT1 was increased.Conclusion:1 The expression level of MNX1-AS1 in ESCC tissues was increased,which was related to lymph node metastasis of ESCC patients.2 After knockdown MNX1-AS1 the capacity of ESCC proliferation,migration and invasion were decreased,and MNX1-AS1 could regulate ESCC cell cycle and apoptosis.MNX1-AS1 may promote ESCC progression through regulating miR-34a/SIRT 1axis. |
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