| Background and objectiveEsophageal cancer(EC),one of the most common malignant tumor types in the world,has high morbidity and mortality rates.Approximately 90% of EC in China are esophageal squamous cell carcinoma(ESCC).The overall 5-year survival rate of ESCC patients is quiet low,which places a heavy burden on society as a whole.The pathogenesis of esophageal cancer has not been elucidated to date,and its occurrence is related to various factors such as abnormal regulation of oncogenes and tumor suppressor genes.Thus,it is of great clinical value and significance to study the molecular mechanism of the genesis and progression of ESCC and to explore the targeted treatment of ESCC.Long non-coding RNAs(lncRNAs)are a class of RNA molecules which have more than 200 nucleotides in length with little or no protein-coding capacity.They exist in the human genome and are widely transcribed.LncRNAs can regulate gene expression through epigenetic modification,transcription and post-transcriptional processing,participating in varieties of biological and pathological processes.A massof studies have shown that lncRNAs not only can play a supervisory role in various diseases,but also dysregulated lncRNAs can serve as a tumor-driven or inhibitory factor.Therefore,exploring the potential molecular mechanism of lncRNAs in ESCC will contribute to understanding the development process of esophageal cancer and developing effective targets for ESCC.The long non-coding RNA MIR31 HG,which located on chromosome 9(9p21.3)of human genome,is named miR-31 host gene.Recent studies have shown that MIR31 HG was upregulated in pancreatic cancer.Knockdown of MIR31 HG could inhibit the proliferation and invasion of pancreatic cancer cells and block the cell cycle.In addition,MIR31 HG was up-regulated in laryngeal squamous cell carcinoma samples and may be a potential biomarker for laryngeal squamous cell carcinoma.These results revealed that MIR31 HG might play an oncogene role in tumors.However,MIR31 HG has not been specifically studied in ESCC.In this study,we detected the expression of MIR31 HG in ESCC tissues and analyzed its relationship with clinicopathological data of ESCC patients.After that,we constructed stable knockdown MIR31 HG cell model to observe the proliferation,migration and invasion of ESCC cells.Moreover,we preliminary explored the molecular mechanism of MIR31 HG in ESCC,providing the experimental and theoretical basis for MIR31 HG as therapeutic target in ESCC treatment.Methods1 The real-time quantitative PCR(qRT-PCR)was performed to detect the expression of MIR31 HG in 53 pairs of ESCC tissues,and the correlation between MIR31 HG and various clinical parameters of ESCC was analyzed.2 Normal esophageal epithelial cells Het-1A,ESCC cells EC9706 and EC1 were cultured.QRT-PCR was performed to detect the expression of MIR31 HG in ESCC cells.ShRNA lentivirus interference technology was used to downregulate MIR31 HG in ESCC cells.WST-1 and transwell experiments were performed to explore the biological function of MIR31 HG silencing on ESCC cells.3 The biological software was used to predict the downstream target gene furin of MIR31 HG.The expression of furin and MMP1 in ESCC tissues were detected byqRT-PCR and the correlation between the level of furin / MMP1 and MIR31 HG was analyzed.Then the levels of furin and MMP1 in ESCC cells before and after transfection were compared to preliminary explore the molecular mechanism of MIR31 HG.Results1 Compared with para-carcinoma tissues,MIR31 HG had a higher expression level in cancer tissues.The expression of MIR31 HG was positively correlated with TNM stage and lymph node metastasis(P<0.05)in ESCC patients,which was not associated with age,sex,location and size of tumor(P> 0.05).2 MIR31 HG was overexpressed in ESCC cells(P<0.05).After knockdown of MIR31 HG,the proliferation numbers of ESCC cells were reduced and their ability of migration and invasion was decreased(P<0.05).3 Furin and MMP1 were upregulated in ESCC tissues,and both of they were positively correlated with the expression of MIR31HG(P <0.05).The knockdown of MIR31 HG downregulated the expression of furin and MMP1(P <0.05).Conclusion1 MIR31 HG was upregulated in ESCC tissues and cells,associating with TNM stage and lymph node metastasis.2 The level change of MIR31 HG could affect the proliferation,migration and invasion of ESCC cells.This process might be achieved through furin / MMP1 pathway.MIR31HG could be a potential therapeutic target for ESCC. |
