CDKN3 mRNA as a biomarker for survival and therapeutic target in cervical cancer
Por:
Barrón E.V., Roman-Bassaure E., Sánchez-Sandoval A.L., Espinosa A.M., Guardado-Estrada M., Medina I., Juárez E., Alfaro A., Bermúdez M., Zamora R., García-Ruiz C., Gomora J.C., Kofman S., Pérez-Armendariz E.M., Berumen J.
Publicada:
15 sep 2015
Resumen:
The cyclin-dependent kinase inhibitor 3 (CDKN3) gene, involved in mitosis, is upregulated in cervical cancer (CC). We investigated CDKN3 mRNA as a survival biomarker and potential therapeutic target for CC. CDKN3 mRNA was measured in 134 CC and 25 controls by quantitative PCR. A 5-year survival study was conducted in 121 of these CC patients. Furthermore, CDKN3-specific siRNAs were used to investigate whether CDKN3 is involved in proliferation, migration, and invasion in CC-derived cell lines (SiHa, CaSki, HeLa). CDKN3 mRNA was on average 6.4-fold higher in tumors than in controls (p = 8 × 10-6, Mann-Whitney). A total of 68.2% of CC patients over expressing CDKN3 gene (fold change = 17) died within two years of diagnosis, independent of the clinical stage and HPV type (Hazard Ratio = 5.0, 95% CI: 2.5-10, p = 3.3 × 10-6, Cox proportional-hazards regression). In contrast, only 19.2% of the patients with lower CDKN3 expression died in the same period. In vitro inactivation of CDKN3 decreased cell proliferation on average 67%, although it had no effect on cell migration and invasion. CDKN3 mRNA may be a good survival biomarker and potential therapeutic target in CC. Copyright: © 2015 Barron et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Filiaciones:
Barrón E.V.:
Univ Nacl Autonoma Mexico, Hosp Gen Mexico, Fac Med, Unidad Med Genom, Mexico City 04510, DF, Mexico
Univ Nacl Autonoma Mexico, Dept Med Expt, Fac Med, Mexico City 04510, DF, Mexico
Roman-Bassaure E.:
Servicio de Oncología, Hospital General de México, México City, Mexico
Sánchez-Sandoval A.L.:
Univ Nacl Autonoma Mexico, Inst Fisiol Celular, Div Neurociencias, Dept Neuropatol Mol, Mexico City 04510, DF, Mexico
Espinosa A.M.:
Univ Nacl Autonoma Mexico, Hosp Gen Mexico, Fac Med, Unidad Med Genom, Mexico City 04510, DF, Mexico
Guardado-Estrada M.:
Univ Nacl Autonoma Mexico, Hosp Gen Mexico, Fac Med, Unidad Med Genom, Mexico City 04510, DF, Mexico
Medina I.:
Univ Nacl Autonoma Mexico, Hosp Gen Mexico, Fac Med, Unidad Med Genom, Mexico City 04510, DF, Mexico
Juárez E.:
Univ Nacl Autonoma Mexico, Hosp Gen Mexico, Fac Med, Unidad Med Genom, Mexico City 04510, DF, Mexico
Alfaro A.:
Univ Nacl Autonoma Mexico, Hosp Gen Mexico, Fac Med, Unidad Med Genom, Mexico City 04510, DF, Mexico
Bermúdez M.:
Univ Nacl Autonoma Mexico, Hosp Gen Mexico, Fac Med, Unidad Med Genom, Mexico City 04510, DF, Mexico
Zamora R.:
Univ Nacl Autonoma Mexico, Inst Invest Biomed, Dept Inmunol, Mexico City 04510, DF, Mexico
García-Ruiz C.:
Univ Nacl Autonoma Mexico, Hosp Gen Mexico, Fac Med, Unidad Med Genom, Mexico City 04510, DF, Mexico
Gomora J.C.:
Univ Nacl Autonoma Mexico, Inst Fisiol Celular, Div Neurociencias, Dept Neuropatol Mol, Mexico City 04510, DF, Mexico
Kofman S.:
Univ Nacl Autonoma Mexico, Hosp Gen Mexico, Fac Med, Serv Genet, Mexico City 04510, DF, Mexico
Pérez-Armendariz E.M.:
Univ Nacl Autonoma Mexico, Dept Med Expt, Fac Med, Mexico City 04510, DF, Mexico
Berumen J.:
Univ Nacl Autonoma Mexico, Dept Med Expt, Fac Med, Mexico City 04510, DF, Mexico
Univ Nacl Autonoma Mexico, Hosp Gen Mexico, Fac Med, Unidad Med Genom, Mexico City 04510, DF, Mexico
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