Tumor suppressor miR-128-3p inhibits metastasis and epithelial-mesenchymal transition by targeting ZEB1 in esophageal squamous-cell cancer

Acta Biochim Biophys Sin (Shanghai). 2018 Feb 1;50(2):171-180. doi: 10.1093/abbs/gmx132.

Abstract

MicroRNAs (miRNAs) are some short RNAs that regulate multiple biological functions at post-transcriptional levels, such as tumorigenic processes, inflammatory lesions and cell apoptosis. Zinc finger E-box binding homeobox factor 1 (ZEB1) is a crucial mediator of epithelial-mesenchymal transition (EMT). It induces malignant progression of various cancers including human esophageal squamous-cell carcinoma (ESCC). In this study, we found that miR-128-3p was downregulated in ESCC tissues and cells by using PCR. Moreover, down-regulated expression of miR-128-3p was testified to be associated with poor prognosis of ESCC patients and might be regarded as an independent prognostic factor. Then, we examined the role of miR-128-3p in ESCC cells, and found that miR-128-3p could suppress the cell migration and invasion in vitro. Furthermore, ZEB1 was confirmed to be a direct target of miR-128-3p by luciferase reporter assay. Rescue experiments proved that EMT was regulated by miR-128-3p via suppression of ZEB1. Taken all together, we conclude that miR-128-3p suppresses EMT and metastasis via ZEB1, and miR-128-3p may be a critical mediator in ESCC.

Keywords: ZEB1; epithelial–mesenchymal transition; esophageal squamous-cell carcinoma; invasion and metastasis; miR-128-3p.

MeSH terms

  • 3' Untranslated Regions / genetics
  • Base Sequence
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / pathology
  • Cell Line
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Epithelial-Mesenchymal Transition / genetics*
  • Esophageal Neoplasms / genetics*
  • Esophageal Neoplasms / metabolism
  • Esophageal Neoplasms / pathology
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Genes, Tumor Suppressor
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • Neoplasm Metastasis
  • Prognosis
  • Sequence Homology, Nucleic Acid
  • Zinc Finger E-box-Binding Homeobox 1 / genetics*
  • Zinc Finger E-box-Binding Homeobox 1 / metabolism

Substances

  • 3' Untranslated Regions
  • MIRN128 microRNA, human
  • MicroRNAs
  • ZEB1 protein, human
  • Zinc Finger E-box-Binding Homeobox 1