MiR-143-3p functions as a tumor suppressor by regulating cell proliferation, invasion and epithelial-mesenchymal transition by targeting QKI-5 in esophageal squamous cell carcinoma

Mol Cancer. 2016 Jun 29;15(1):51. doi: 10.1186/s12943-016-0533-3.

Abstract

Background: Dysregulation of microRNAs (miRNAs) have been demonstrated to contribute to carcinogenesis. MiR-143-3p has been identified to function as a tumor suppressor in several tumors, but the role of miR-143-3p in esophageal squamous cell carcinoma (ESCC) has not been intensively investigated. Our aim was to evaluate the potential role of miR-143-3p in the progression of ESCC.

Methods: The expression levels of miR-143-3p and QKI-5 protein were measured in 80 resected ESCC tumor specimens and the clinicopathological significance of these levels determined. We also investigated the role of miR-143-3p in the regulation of QKI-5 expression in ESCC cell lines both in vivo and in vitro.

Results: MiR-143-3p levels were decreased in ESCC clinical samples and low expression of miR-143-3p was significantly associated with poor prognosis in ESCC patients. Ectopic expression of miR-143-3p suppressed proliferation and induced apoptosis in ESCC cells both in vivo and in vitro. Ectopic expression of miR-143-3p also reduced the metastatic potential of cells by selectively regulating epithelial-mesenchymal transition regulatory proteins. Furthermore, QKI-5 isoform was upregulated in ESCC tissues and was a direct target of miR-143-3p. Lastly, re-introduction of QKI-5 expression abrogated the inhibitory effects of miR-143-3p on ESCC cell proliferation and motility.

Conclusions: Our results demonstrate that miR-143-3p acts as a tumor-suppressor by targeting QKI-5 in ESCC, suggesting that miR-143-3p is a potential therapy for the treatment of ESCC.

Keywords: Esophageal squamous cell carcinoma; Invasion; MiR-143-3p; Proliferation; QKI-5.

Publication types

  • Retracted Publication

MeSH terms

  • 3' Untranslated Regions
  • Adult
  • Aged
  • Animals
  • Apoptosis
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / pathology*
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Disease Models, Animal
  • Epithelial-Mesenchymal Transition / genetics*
  • Esophageal Neoplasms / genetics*
  • Esophageal Neoplasms / metabolism
  • Esophageal Neoplasms / pathology*
  • Esophageal Squamous Cell Carcinoma
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • Gene Knockdown Techniques
  • Genes, Tumor Suppressor*
  • Heterografts
  • Humans
  • Male
  • Mice
  • MicroRNAs / genetics*
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Metastasis
  • Neoplasm Staging
  • RNA Interference*
  • RNA-Binding Proteins / genetics*

Substances

  • 3' Untranslated Regions
  • MIRN143 microRNA, human
  • MicroRNAs
  • QKI protein, human
  • RNA-Binding Proteins