HOXC13 promotes proliferation of esophageal squamous cell carcinoma via repressing transcription of CASP3

Cancer Sci. 2018 Feb;109(2):317-329. doi: 10.1111/cas.13453. Epub 2017 Dec 20.

Abstract

Esophageal squamous cell carcinoma (ESCC), the dominant subtype of esophageal cancer, is one of the most common digestive tumors worldwide. In this study, we confirmed that HOXC13, a member of the homeobox HOXC gene family, was significantly upregulated in ESCC and its overexpression was associated with poorer clinical characteristics and worse prognosis. Moreover, knockdown of HOXC13 inhibited proliferation and induced apoptosis of ESCC through upregulating CASP3. ChIP analysis revealed that HOXC13 repressed transcription of CASP3 through directly targeting the promotor region of CASP3. We also found that miR-503 downregulated HOXC13, by directly targeting its 3'UTR, and inhibited proliferation of ESCC. In conclusion, our study demonstrates that HOXC13, which is directly targeted by miR-503, promotes proliferation and inhibits apoptosis of ESCC through repressing transcription of CASP3.

Keywords: CASP3; HOXC13; apoptosis; esophageal squamous cell carcinoma; miR-503.

MeSH terms

  • Animals
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / pathology*
  • Caspase 3 / genetics*
  • Caspase 3 / metabolism
  • Cell Line, Tumor
  • Cell Proliferation
  • Down-Regulation*
  • Esophageal Neoplasms / genetics
  • Esophageal Neoplasms / metabolism
  • Esophageal Neoplasms / pathology*
  • Esophageal Squamous Cell Carcinoma
  • Female
  • Gene Expression Regulation, Neoplastic
  • Homeodomain Proteins / genetics*
  • Homeodomain Proteins / metabolism
  • Humans
  • Male
  • Mice
  • MicroRNAs / genetics*
  • Neoplasm Transplantation
  • Prognosis
  • Promoter Regions, Genetic
  • Survival Analysis
  • Transcription, Genetic
  • Up-Regulation

Substances

  • HOXC13 protein, human
  • Homeodomain Proteins
  • MIRN503 microRNA, human
  • MicroRNAs
  • CASP3 protein, human
  • Caspase 3