HMGA1 and HMGA2 expression and comparative analyses of HMGA2, Lin28 and let-7 miRNAs in oral squamous cell carcinoma

BMC Cancer. 2014 Sep 23:14:694. doi: 10.1186/1471-2407-14-694.

Abstract

Background: Humans and dogs are affected by squamous cell carcinomas of the oral cavity (OSCC) in a considerably high frequency. The high mobility group A2 (HMGA2) protein was found to be highly expressed in human OSCC and its expression was suggested to act as a useful predictive and prognostic tool in clinical management of oral carcinomas. Herein the expression of HMGA2 and its sister gene HMGA1 were analysed within human and canine OSCC samples. Additionally, the HMGA negatively regulating miRNAs of the let-7 family as well as the let-7 regulating gene Lin28 were also comparatively analysed. Deregulations of either one of these members could affect the progression of human and canine OSCC.

Methods: Expression levels of HMGA1, HMGA2, Lin28, let-7a and mir-98 were analysed via relative qPCR in primary human and canine OSCC, thereof derived cell lines and non-neoplastic samples. Additionally, comparative HMGA2 protein expression was analysed by immunohistochemistry.

Results: In both species, a significant up-regulation of the HMGA2 gene was found within the neoplastic samples while HMGA1 expression did not show significant deregulations. Comparative analyses showed down-regulation of mir-98 in human samples and up-regulation of let-7a and mir-98 in canine neoplastic samples. HMGA2 immunostainings showed higher intensities within the invasive front of the tumours than in the centre of the tumour in both species.

Conclusions: HMGA2 could potentially serve as tumour marker in both species while HMGA1 might play a minor role in OSCC progression. Comparative studies indicate an inverse correlation of HMGA2 and mir-98 expression in human samples whereas in dogs no such characteristic could be found.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Animals
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / veterinary*
  • Cell Line, Tumor
  • Dog Diseases / genetics
  • Dog Diseases / metabolism*
  • Dogs
  • Female
  • Gene Expression
  • HMGA1a Protein / genetics
  • HMGA1a Protein / metabolism
  • HMGA1b Protein / genetics
  • HMGA1b Protein / metabolism
  • HMGA2 Protein / genetics
  • HMGA2 Protein / metabolism*
  • Humans
  • Male
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • Mouth Neoplasms / genetics
  • Mouth Neoplasms / metabolism
  • Mouth Neoplasms / veterinary*
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*

Substances

  • Biomarkers, Tumor
  • HMGA2 Protein
  • Lin28A protein, human
  • MIRN98 microRNA, human
  • MicroRNAs
  • RNA-Binding Proteins
  • mirnlet7 microRNA, human
  • HMGA1b Protein
  • HMGA1a Protein