MicroRNA-140 Represses Esophageal Cancer Progression via Targeting ZEB2 to Regulate Wnt/β-Catenin Pathway

Background: MicroRNAs have been reported to play regulatory functions in various cancers, including esophageal cancer. The aim of this study was to investigate the effects of miR140 on the progression of esophageal cancer and the underlying regulatory mechanism. Methods: The levels of miR-140 and zinc finger E-box-binding homeobox 2 (ZEB2) messenger RNA in esophageal cancer tissues and cell lines were measured by quantitative real-time polymerase chain reaction. The protein levels of ZEB2, beta-catenin, c-Myc, and cyclinD1 were determined by Western blot. Cell proliferation and apoptosis were determined by 3(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay and flow cytometry, respectively. Cell migration and invasion were assessed by transwell assay. In addition, the relationship between miR-140 and ZEB2 was predicted by TargetScan online database and confirmed by dual-luciferase reporter assay. The tumor xenograft model was used to verify the role of miR-140 in esophageal cancer progression in vivo. Results: The expression of miR-140 was downregulated whereas ZEB2 expression was upregulated in esophageal cancer tissues compared with paracancerous normal tissues. Functionally, both miR-140 overexpression and ZEB2 knockdown inhibited proliferation, migration, and invasion and induced apoptosis in esophageal cancer cells. ZEB2 over expression reversed the effects of miR-140 on proliferation, apoptosis, migration, and invasion of esophageal cancer cells. Mechanistically, ZEB2 was identified as a target of miR140. Furthermore, miR-140 suppressed Wnt/beta-catenin pathway by regulating ZEB2 expression in esophageal cancer cells. MiR-140 inhibited tumor growth of esophageal cancer through repressing ZEB2 expression in vivo. Conclusions: Our results demonstrated that miR-140 inhibited esophageal cancer development by targeting ZEB2 through inactivating Wnt/beta-catenin pathway. (c) 2020 Elsevier Inc. All rights reserved.

Automated summary

The study demonstrated that miR-140 inhibited the development of esophageal cancer by targeting ZEB2 and inactivating the Wnt/β-catenin pathway, both in vitro and in vivo.