miR-452-5p promotes the proliferation, invasion and EMT of esophageal cancerKYSE-150 cells via targeting SOX7
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Abstract:
Objective: To detect the expression of miR-452-5p in esophageal squamous cell cancer (ESCC) tissues, and to explore the effect of aberrant miR-452-5p expression on the proliferation, invasion and EMT process of esophageal cancer KYSE-150 cells as well as the possible molecular mechanism. Methods: Cancer tissue samples and corresponding paracancerous tissues were collected from 86 ESCC patients treated at the Fourth Hospital of Hebei Medical University from March 2012 to December 2015. The expression levels of miR-452-5p and other related genes were detected by qPCR method. KYSE-150 cells were transfected with miR-452-5p mimic or pcDNA3.1- SOX7 to construct over-expressed cell lines. Analysis of the relationship between miR-452-5p expression and ESCC pathological features and 5-year OS of patients. MTS and transwell assay were performed to assess the effect of miR-452-5p over-expression on proliferation, invasion and EMT progress of KYSE-150 cells. The interaction between miR-452-5p and SRY-box transcription factor 7 (SOX7)3'UTR and the activation of Wnt/β-catenin pathway were detected by Dual-luciferase reporter gene assay andTOP/FOPreporter gene system. Results: The expression of miR-452-5p was significantly up-regulated in ESCC tissues (P<0.01). High expression of miR-452-5p was correlated with the lymph node metastasis, TNM stage and the 5-year OS of ESCC patients (all P<0.01). Over-expression of miR-452-5p significantly promoted proliferation, invasion ability and the EMT process in KYSE-150 cells (P<0.05 or P<0.01). SOX7 was predicted to be the direct target gene of miR-452-5p. miR-452-5p affected the activation level of Wnt pathway through targeted regulation of SOX7 (P<0.05 or P<0.01).At the same time, the expression of miR-452-5p was also regulated by the activation level of Wnt pathway, and miR-452-5p might be a downstream target gene of Wnt pathway (P<0.05 or P<0.01). Conclusion: miR-452-5p promotes the activation level of Wnt pathway through miR-452-5p/SOX7/Wnt/miR-452-5p positive feedback loop, which further promoting the proliferation, invasion and the EMT process of esophageal cancer KYSE-150 cells. miR-452-5p is expected to be a potential target for molecular therapy and a novel molecular markerfortheprognosisevaluationofESCCpatients.