Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
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HOXA9 is Underexpressed in Cervical Cancer Cells and its Restoration Decreases Proliferation, Migration and Expression of Epithelial-to-Mesenchymal Transition Genes

  • Alvarado-Ruiz, Liliana (Doctorado en Ciencias Biomedicas, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara) ;
  • Martinez-Silva, Maria Guadalupe (Servicio de Patologia, Centro Medico Nacional de Occidente, IMSS) ;
  • Torres-Reyes, Luis Alberto (Doctorado en Ciencias Biomedicas, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara) ;
  • Pina-Sanchez, Patricia (Laboratorio de Oncologia Genomica, Unidad de Investigacion Medica en Enfermedades Oncologicas(UIMEO), Centro Medico Nacional Siglo XXI (CMN-SXXI)-IMSS) ;
  • Ortiz-Lazareno, Pablo (Division of Immunology, Molecular Immunology, Centro de Investigacion Biomedica de Occidente, IMSS) ;
  • Bravo-Cuellar, Alejandro (Division of Immunology, Molecular Immunology, Centro de Investigacion Biomedica de Occidente, IMSS) ;
  • Aguilar-Lemarroy, Adriana (Division of Immunology, Molecular Immunology, Centro de Investigacion Biomedica de Occidente, IMSS) ;
  • Jave-Suarez, Luis Felipe (Division of Immunology, Molecular Immunology, Centro de Investigacion Biomedica de Occidente, IMSS)
  • Published : 2016.04.11
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Abstract

HOX transcription factors are evolutionarily conserved in many different species and are involved in important cellular processes such as morphogenesis, differentiation, and proliferation. They have also recently been implicated in carcinogenesis, but their precise role in cancer, especially in cervical cancer (CC), remains unclear. In this work, using microarray assays followed by the quantitative polymerase chain reaction (qPCR), we found that the expression of 25 HOX genes was downregulated in CC derived cell lines compared with non-tumorigenic keratinocytes. In particular, the expression of HOXA9 was observed as down-modulated in CC-derived cell lines. The expression of HOXA9 has not been previously reported in CC, or in normal keratinocytes of the cervix. We found that normal CC from women without cervical lesions express HOXA9; in contrast, CC cell lines and samples of biopsies from women with CC showed significantly diminished HOXA9 expression. Furthermore, we found that methylation at the first exon of HOXA9 could play an important role in modulating the expression of this gene. Exogenous restoration of HOXA9 expression in CC cell lines decreased cell proliferation and migration, and induced an epithelial-like phenotype. Interestingly, the silencing of human papilloma virus (HPV) E6 and E7 oncogenes induced expression of HOXA9. In conclusion, controlling HOXA9 expression appears to be a necessary step during CC development. Further studies are needed to delineate the role of HOXA9 during malignant progression and to afford more insights into the relationship between downmodulation of HOXA9 and viral HPV oncoprotein expression during cercical cancer development.

Keywords

References

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