HMGA2 is down-regulated by microRNA let-7 and associated with epithelial-mesenchymal transition in oesophageal squamous cell carcinomas of Kazakhs

Histopathology. 2014 Sep;65(3):408-17. doi: 10.1111/his.12401. Epub 2014 May 12.

Abstract

Aims: To investigate the expression of let-7 and its regulation of high-mobility group A2 protein (HMGA2), and to verify the relationship between let-7, HMGA2 and the process of epithelial-mesenchymal transition (EMT), in oesophageal squamous cell carcinomas (OSCC) of Kazakh patients.

Methods and results: Expression of let-7 was significantly lower in Eca109 cells than in normal oesophageal squamous epithelium (P = 2.4 × 10(-7) ). Increased accumulation of let-7 after transfection of Eca109 cells with synthetic let-7 inhibited cell proliferation. Let-7 could repress expression of HMGA2 after co-transfection with let-7 and HMGA2 (P = 0.002). Moreover, let-7 expression was observed less frequently (P = 2.0 × 10(-8) ), and HMGA2 expression more frequently (P = 1.0 × 10(-10) ), in OSCC than in normal adjacent tissues; and let-7 expression was observed less frequently in OSCC from Kazakh patients than in those from Han and Uygur patients (P = 0.041). There was a reverse correlation between expression of let-7 and HMGA2 (P = 0.018). Expression of Snail was statistically higher in Kazakhs' OSCC (P = 0.029), and was correlated with depth of invasion (P = 0.021) and HMGA2 expression (P = 0.026).

Conclusions: Expression of let-7 can suppress cell proliferation by acting directly on regulation of HMGA2 in OSCC. High expression of Snail and its correlation with HMGA2 expression and tumour invasion suggest that HMGA2 may be involved in EMT in the OSCC of Kazakh patients.

Keywords: Kazakh; Snail; high-mobility group A2 protein; let-7; oesophageal squamous cell carcinoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / pathology*
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • China
  • Down-Regulation
  • Epithelial-Mesenchymal Transition / genetics*
  • Esophageal Neoplasms / genetics*
  • Esophageal Neoplasms / metabolism
  • Esophageal Neoplasms / pathology*
  • Esophageal Squamous Cell Carcinoma
  • Ethnicity / genetics
  • Female
  • HMGA2 Protein / genetics*
  • HMGA2 Protein / metabolism
  • Humans
  • Immunohistochemistry
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • Snail Family Transcription Factors
  • Transcription Factors / metabolism

Substances

  • HMGA2 Protein
  • MicroRNAs
  • Snail Family Transcription Factors
  • Transcription Factors
  • mirnlet7 microRNA, human