LncRNA H19 Downregulate Let-7 Promote Epithelial-mensenchymal Transition In Esophageal Squamous Cell Carcinoma

Objective: To explore the interaction between H19 and microRNA let-7 and the role of H19 in esophageal squamous cell carcinoma(ESCC)epithelial mesenchymal transformation(EMT),and to reveal the function of LncRNA H19 in esophageal squamous cell carcinoma migration and invasion.Methods: In ESCC tissue,using qRT-PCR to detect the relative expression of H19 and let-7 in 48 esophageal squamous carcinoma tissues and adjacent normal tissues.Analysis the association between H19 expression and let-7 expression,and whether H19 expression is correlated to patients’ clinical pathologic features.In ESCC cell lines,using qRT-PCR to detect H19 and let-7 background expression,and choose the KYSE30 and Eca109 which high expression of H19 to transfected with H19 siRNA.Then the relative expression of H19 and let-7 is tested by qRT-PCR,and the expression of EMT related molecular is detected by Western blot.MTT was used to detected the effect of H19 on cell proliferation,flow cytometry was used to detected the early stage apoptosis rate,wound heading assay and Transwell assay were used to detected the cell migration and invasion,respectively.Results: H19 is overexpression in ESCC tissues(1.90±1.94),compared with adjacent normal tissues(P<0.05).ESCC tissues with high expression of H19 which let-7 is low expression(P<0.05).H19 expression is positive correlation with ESCC invasion depth(P<0.05),and high expression of H19 indicates poor outcome(P<0.05).In KYSE30 and Eca109,knockdown H19 successfully(P<0.05)would upregulate let-7(P<0.05),especially in KYSE30(4.65±0.21).Western blot reveals that downregulate H19 would upregulate E-cadherin(2.07±0.17),downregulate Vimentin(0.04±0.01),β-catenin(0.51±0.04,0.56±0.10),and Slug(0.36±0.08,0.37±0.06).Knockdown H19 in ECSS cell lines restrain cell proliferation(P<0.05),migration(P<0.05),and invasion(P<0.05),while accelerate cell apoptosis(P<0.05).Conclusion: Our study demonstrated that LncRNA H19 has the role of downregulate let-7 and promote ESCC EMT so as to activate tumor malignant proliferation,invasion and metastasis.The expression of LncRNA H19 can be a biomarker in ESCC prognosis.